National Library of Energy BETA

Sample records for outsmarting flu viruses

  1. Outsmarting the art of camouflage

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Outsmarting the art of camouflage Outsmarting the art of camouflage It's not just soldiers that use camouflage to blend into their surroundings. Facilities and the movement of people and equipment can be camouflaged. These can present significant challenges to the military. How can we see what doesn't want to be seen? November 7, 2016 Copperhead Snake on Dead Leaves, watercolor by Abbott Handerson Thayer (1849-1921) Copperhead Snake on Dead Leaves, watercolor by Abbott Handerson Thayer

  2. Toward Design of a Universal Flu Vaccine

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Print Worldwide, influenza causes substantial deaths and yearly economic burdens, but the highly changeable nature of the flu virus ...

  3. Toward Design of a Universal Flu Vaccine

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Print Worldwide, influenza causes substantial deaths and yearly economic burdens, but the highly changeable nature of the flu virus...

  4. From the development of exotic materials to the study of flu virus

    Office of Scientific and Technical Information (OSTI)

    shuttles, Iowa State University and DOE partnership is on the move | OSTI, US Dept of Energy Office of Scientific and Technical Information From the development of exotic materials to the study of flu virus shuttles, Iowa State University and DOE partnership is on the move Back to the OSTI News Listing for 2011 Iowa State University's vision is to lead the world in advancing the land-grant ideas of putting science, technology, and human creativity to work. A unique partnership with Ames Lab

  5. Avian Flu

    SciTech Connect

    Eckburg, Paul

    2006-11-06

    Since 2003, a severe form of H5N1 avian influenza has rapidly spread throughout Asia and Europe, infecting over 200 humans in 10 countries. The spread of H5N1 virus from person-to-person has been rare, thus preventing the emergence of a widespread pandemic. However, this ongoing epidemic continues to pose an important public health threat. Avian flu and its pandemic potential in humans will be discussed.

  6. Structure and Receptor Specificity of an Avian Flu Antigen

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Structure and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three...

  7. Structure and Receptor Specificity of an Avian Flu Antigen

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    and Receptor Specificity of an Avian Flu Antigen Print To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three continents,...

  8. From the development of exotic materials to the study of flu...

    Office of Scientific and Technical Information (OSTI)

    From the development of exotic materials to the study of flu virus shuttles, Iowa State University and DOE partnership is on the move Back to the OSTI News Listing for 2011 Iowa ...

  9. The forecast calls for flu

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Science on the Hill: The forecast calls for flu Using mathematics, computer programs, ... We're getting close. Using mathematics, computer programs, statistics and information ...

  10. Picture of the Week: Fighting the flu, one cell at a time

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    0 Fighting the flu, one cell at a time To better understand autophagy in influenza A virus replication, a team of scientists from Los Alamos' Biosecurity and Public Health group are taking a closer look at the role of Beclin-1, one of the key protein players in this intricate game of cellular life and death. August 1, 2016 Fighting the flu, one cell at a time x Fighting the flu, one cell at a time Fluorescent microscopy images taken at Los Alamos National Laboratory dramatize the battleground

  11. Toward Design of a Universal Flu Vaccine

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Toward Design of a Universal Flu Vaccine Toward Design of a Universal Flu Vaccine Print Wednesday, 30 January 2013 00:00 Worldwide, influenza causes substantial deaths and yearly ...

  12. Flu Shot Clinic | The Ames Laboratory

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Flu Shot Clinic Event Type: Lab Wide Date: 10/10/2016 - 09:00 Location: 205 TASF Flu shots are provided at no cost to the following employee groups: Faculty Professional and scientific Merit Post docs ISU Foundation Iowa State Daily Retirees on university health plans who are not yet 65 Undergraduate and graduate students and visiting scholars are not eligible to receive flu shots at the clinic. These individuals should contact Thielen Student Health Center, 294-5801, for flu vaccine

  13. Our view: Vaccinate now, prevent flu later

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Our view: Vaccinate now, prevent flu later Our view: Vaccinate now, prevent flu later Los Alamos National Laboratory scientists are predicting that this winter's flu season is most likely to peak in February across much of the United States. The scientists can say this because of the model they have constructed. December 24, 2015 Man sneezing Model suggests still time to get your flu shot and be protected. "There's no crystal ball when it comes to predicting disease outbreaks," said

  14. Picture of the Week: Forecasting Flu

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    3 Forecasting Flu What if we could forecast infectious diseases the same way we forecast the weather, and predict how diseases like Dengue, Typhus or Zika were going to spread? March 6, 2016 flu epidemics modellled using social media Watch the video on YouTube. Forecasting Flu What if we could forecast infectious diseases the same way we forecast the weather, and predict how diseases like Dengue, Typhus or Zika were going to spread? Using real-time data from Wikipedia and social media, Sara del

  15. Our view: Vaccinate now, prevent flu later

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    the Los Alamos scientist who leads the project. "Holiday travel and the rate at which people get flu shots can change the forecast, so we'll continue to update the model as ...

  16. Our view: Vaccinate now, prevent flu later

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    scientists can say this because of the model they have constructed. December 24, 2015 Man sneezing Model suggests still time to get your flu shot and be protected. "There's no...

  17. Occ. Med. Offers Staff Flu Vaccines by Appointment | Jefferson...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Occ. Med. Offers Staff Flu Vaccines by Appointment Occupational Medicine is now accepting appointments from Jefferson Lab staff for Influenza vaccinations. If you would like to be...

  18. Point-of-Care Flu Diagnosis | GE Global Research

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    and InDevR Scientists Improve Flu Diagnoses Click to email this to a friend (Opens in new window) Share on Facebook (Opens in new window) Click to share (Opens in new window) Click ...

  19. Flu shots available beginning Oct. 5 | The Ames Laboratory

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    battle the flu Wash hands regularly with soap and water, use hand sanitizer Sneeze and cough into a sleeve or tissue Stay home when sick Regularly sanitize work surfaces and...

  20. February most likely month for flu season to peak

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    the Los Alamos scientist who leads the project. "Holiday travel and the rate at which people get flu shots can change the forecast, so we'll continue to update the model as ...

  1. Occ. Med. Currently Offering Staff the Flu Vaccine by Appointment |

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Jefferson Lab Occ. Med. Currently Offering Staff the Flu Vaccine by Appointment Occ. Med. Currently Offering Staff the Flu Vaccine by Appointment Occupational Medicine is now accepting appointments from Jefferson Lab staff for Influenza vaccinations. If you would like to be vaccinated, please contact Johnie Banks, Occupational Medicine at ext. 7539 to schedule an appointment. Please keep in mind that for 15 minutes after vaccination you should remain at Jefferson Lab, in the presence of

  2. Fast pandemic detection tool ready to fight flu

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Fast pandemic detection tool ready to fight flu Fast pandemic detection tool ready to fight flu Researchers are developing new tools for rapidly characterizing biological pathogens that could give rise to potentially deadly pandemics such as Influenza A (H1N1). June 9, 2009 Los Alamos National Laboratory sits on top of a once-remote mesa in northern New Mexico with the Jemez mountains as a backdrop to research and innovation covering multi-disciplines from bioscience, sustainable energy sources,

  3. Toward Design of a Universal Flu Vaccine

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    large structural differences from CR9114, indicating that, while they bind to a similar region on various viruses, they employ different strategies for neutralizing those...

  4. City of Chicago won't sweat the flu with Argonne's help | Argonne...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    on their toes." This particular exercise followed the spread of an imaginary flu from Egypt. By the time the flu "arrived" in Chicago, more than 15,000 cases had been reported...

  5. Microsoft Word - 1918flu.doc

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Figure 1. Ribbon representation of the hemagglutinin HA0 trimer from the 1918 influenza virus. Each monomer possesses two important sites: 1) the 'Receptor binding site' (blue shade) for virus attachment to the host lung epithelial cells via sialic acid containing host cell receptors. 2) the 'Cleavage site' where for full infectivity, the single chain (HA0) is cut into two chains (HA1 colored red and HA2 colored green). At the N-terminal end of the HA2 chain is the fusion peptide which is

  6. Full-spectrum disease response : beyond just the flu.

    SciTech Connect

    Knazovich, Michael Ward; Cox, Warren B.; Henderson, Samuel Arthur

    2010-04-01

    Why plan beyond the flu: (1) the installation may be the target of bioterrorism - National Laboratory, military base collocated in large population center; and (2) International Airport - transport of infectious agents to the area - Sandia is a global enterprise and staff visit many foreign countries. In addition to the Pandemic Plan, Sandia has developed a separate Disease Response Plan (DRP). The DRP addresses Category A, B pathogens and Severe Acute Respiratory Syndrome (SARS). The DRP contains the Cities Readiness Initiative sub-plan for disbursement of Strategic National Stockpile assets.

  7. Structural Basis of Preexisting Immunity to the 2009 H1N1 Pandemic Influenza Virus

    SciTech Connect

    Xu, Rui; Ekiert, Damian C.; Krause, Jens C.; Hai, Rong; Crowe, Jr., James E.; Wilson, Ian A.

    2010-05-25

    The 2009 H1N1 swine flu is the first influenza pandemic in decades. The crystal structure of the hemagglutinin from the A/California/04/2009 H1N1 virus shows that its antigenic structure, particularly within the Sa antigenic site, is extremely similar to those of human H1N1 viruses circulating early in the 20th century. The cocrystal structure of the 1918 hemagglutinin with 2D1, an antibody from a survivor of the 1918 Spanish flu that neutralizes both 1918 and 2009 H1N1 viruses, reveals an epitope that is conserved in both pandemic viruses. Thus, antigenic similarity between the 2009 and 1918-like viruses provides an explanation for the age-related immunity to the current influenza pandemic.

  8. Structure and Receptor Specificity of an Avian Flu Antigen

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    combined effects could allow the Viet04 virus to escape entrapment by mucins in the lungs and increase binding to susceptible human epithelial cells. These mutations therefore...

  9. Simulating the "zombie virus" spreading through Chicago | Argonne

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    National Laboratory Simulating the "zombie virus" spreading through Chicago Share Topic Security Decision science Emergency & disaster management VIDEO DESCRIPTION: Argonne researcher Chick Macal and his team spend their days building mathematical models to simulate the spread of disease, like flu, Ebola and MRSA, through populations. This helps officials and policymakers address ongoing crises and prepare for potential ones. But this fall, they put a different virus through

  10. Outsmarting neural networks: an alternative paradigm for machine learning

    SciTech Connect

    Protopopescu, V.; Rao, N.S.V.

    1996-10-01

    We address three problems in machine learning, namely: (i) function learning, (ii) regression estimation, and (iii) sensor fusion, in the Probably and Approximately Correct (PAC) framework. We show that, under certain conditions, one can reduce the three problems above to the regression estimation. The latter is usually tackled with artificial neural networks (ANNs) that satisfy the PAC criteria, but have high computational complexity. We propose several computationally efficient PAC alternatives to ANNs to solve the regression estimation. Thereby we also provide efficient PAC solutions to the function learning and sensor fusion problems. The approach is based on cross-fertilizing concepts and methods from statistical estimation, nonlinear algorithms, and the theory of computational complexity, and is designed as part of a new, coherent paradigm for machine learning.

  11. Novel use of flu surveillance data: Evaluating potential of sentinel populations for early detection of influenza outbreaks

    DOE PAGES [OSTI]

    Daughton, Ashlynn R.; Velappan, Nileena; Abeyta, Esteban; Priedhorsky, Reid; Deshpande, Alina; Turner, Stephen J.

    2016-07-08

    Influenza causes significant morbidity and mortality each year, with 2–8% of weekly outpatient visits around the United States for influenza-like-illness (ILI) during the peak of the season. Effective use of existing flu surveillance data allows officials to understand and predict current flu outbreaks and can contribute to reductions in influenza morbidity and mortality. Previous work used the 2009–2010 influenza season to investigate the possibility of using existing military and civilian surveillance systems to improve early detection of flu outbreaks. Results suggested that civilian surveillance could help predict outbreak trajectory in local military installations. To further test that hypothesis, we comparemore » pairs of civilian and military outbreaks in seven locations between 2000 and 2013. We find no predictive relationship between outbreak peaks or time series of paired outbreaks. This larger study does not find evidence to support the hypothesis that civilian data can be used as sentinel surveillance for military installations. We additionally investigate the effect of modifying the ILI case definition between the standard Department of Defense definition, a more specific definition proposed in literature, and confirmed Influenza A. We find that case definition heavily impacts results. In conclusion, this study thus highlights the importance of careful selection of case definition, and appropriate consideration of case definition in the interpretation of results.« less

  12. Generating electricity from viruses

    SciTech Connect

    Lee, Seung-Wuk

    2013-10-31

    Berkeley Lab's Seung-Wuk Lee discusses "Generating electricity from viruses" in this Oct. 28, 2013 talk, which is part of a Science at the Theater event entitled Eight Big Ideas.

  13. Generating electricity from viruses

    ScienceCinema

    Lee, Seung-Wuk

    2014-06-23

    Berkeley Lab's Seung-Wuk Lee discusses "Generating electricity from viruses" in this Oct. 28, 2013 talk, which is part of a Science at the Theater event entitled Eight Big Ideas.

  14. Second Round of Small Business Vouchers Pilot Awards 3 Small...

    Energy Saver

    Outsmart Power Systems, Natick, Massachusetts: OutSmart will leverage work with the labs to expand and develop demand side management and demand response markets. Working with ...

  15. Production of virus resistant plants

    DOEpatents

    Dougherty, William G.; Lindbo, John A.

    1996-01-01

    A method of suppressing virus gene expression in plants using untranslatable plus sense RNA is disclosed. The method is useful for the production of plants that are resistant to virus infection.

  16. Production of virus resistant plants

    DOEpatents

    Dougherty, W.G.; Lindbo, J.A.

    1996-12-10

    A method of suppressing virus gene expression in plants using untranslatable plus sense RNA is disclosed. The method is useful for the production of plants that are resistant to virus infection. 9 figs.

  17. An introduction to computer viruses

    SciTech Connect

    Brown, D.R.

    1992-03-01

    This report on computer viruses is based upon a thesis written for the Master of Science degree in Computer Science from the University of Tennessee in December 1989 by David R. Brown. This thesis is entitled An Analysis of Computer Virus Construction, Proliferation, and Control and is available through the University of Tennessee Library. This paper contains an overview of the computer virus arena that can help the reader to evaluate the threat that computer viruses pose. The extent of this threat can only be determined by evaluating many different factors. These factors include the relative ease with which a computer virus can be written, the motivation involved in writing a computer virus, the damage and overhead incurred by infected systems, and the legal implications of computer viruses, among others. Based upon the research, the development of a computer virus seems to require more persistence than technical expertise. This is a frightening proclamation to the computing community. The education of computer professionals to the dangers that viruses pose to the welfare of the computing industry as a whole is stressed as a means of inhibiting the current proliferation of computer virus programs. Recommendations are made to assist computer users in preventing infection by computer viruses. These recommendations support solid general computer security practices as a means of combating computer viruses.

  18. From Shakespeare to Viruses

    ScienceCinema

    Kim, Sung-Hou

    2013-05-29

    Berkeley Lab scientists have created a unique new tool for analyzing and comparing long sets of data, be it the genomes of mammals or viruses, or the works of Shakespeare. The results of the Shakespeare analysis surprised scholars with their accuracy.

  19. From Shakespeare to Viruses

    ScienceCinema

    Sung-Hou Kim

    2010-01-08

    Berkeley Lab scientists have created a unique new tool for analyzing and comparing long sets of data, be it the genomes of mammals or viruses, or the works of Shakespeare. The results of the Shakespeare analysis surprised scholars with their accuracy

  20. Computer virus information update CIAC-2301

    SciTech Connect

    Orvis, W.J.

    1994-01-15

    While CIAC periodically issues bulletins about specific computer viruses, these bulletins do not cover all the computer viruses that affect desktop computers. The purpose of this document is to identify most of the known viruses for the MS-DOS and Macintosh platforms and give an overview of the effects of each virus. The authors also include information on some windows, Atari, and Amiga viruses. This document is revised periodically as new virus information becomes available. This document replaces all earlier versions of the CIAC Computer virus Information Update. The date on the front cover indicates date on which the information in this document was extracted from CIAC`s Virus database.

  1. Science Summary

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Liddington Research Burnham News Release Dana-Farber Cancer Institute Centers for Disease Control and Prevention » Videos Attacking Influenza Scientists Identify Antibodies Super Flu Vaccine » Share this Article Laboratree Ologeez SciLink LabSpaces Scientists Identify Achilles' Heel of Flu Viruses Scientists have recently identified a family of human antibodies that can take out an unprecedented number of different types of flu viruses, including H5N1 'bird flu' and the 1918 H1N1 'Spanish

  2. Stanford Synchrotron Radiation Lightsource

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    the design principles of natural functional sites. The team targeted a surface on the influenza hemagglutinin protein that enables flu viruses to attach to and invade cells lining...

  3. Immunogenic compositions comprising human immunodeficiency virus...

    Office of Scientific and Technical Information (OSTI)

    Patent: Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins Citation Details In-Document Search Title: Immunogenic compositions comprising...

  4. Recombinant herpes simplex virus useful for treating neoplastic disease

    DOEpatents

    Whitley, Richard J.; Roizman, Bernard

    2010-06-29

    Recombinant herpes simplex viruses comprising DNA encoding cytokines and methods for treating neoplastic diseases using the inventive recombinant viruses are disclosed.

  5. Structure and Mutagenesis of the Parainfluenza Virus 5Hemagglutinin...

    Office of Scientific and Technical Information (OSTI)

    Journal Article: Structure and Mutagenesis of the Parainfluenza Virus 5 ... Title: Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase ...

  6. Human immunodeficiency virus type 1 clade M mosaic gag polypeptides...

    Office of Scientific and Technical Information (OSTI)

    Patent: Human immunodeficiency virus type 1 clade M mosaic gag polypeptides Citation Details In-Document Search Title: Human immunodeficiency virus type 1 clade M mosaic gag ...

  7. Structure of the Newcastle disease virus hemagglutinin-neuraminidase...

    Office of Scientific and Technical Information (OSTI)

    virus hemagglutinin-neuraminidase (HN) ectodomain reveals a four-helix bundle stalk Citation Details In-Document Search Title: Structure of the Newcastle disease virus ...

  8. Presentation, Zika Virus Disease and Prevention

    Energy.gov [DOE]

    “Zika Virus Disease and Prevention” presentation was made by Bonnie S. Richter, MPH, PhD, at the May 19 Office of Environment, Health, Safety and Security (EHSS) All Hands Meeting.

  9. Zika Virus Disease and Prevention Presentation

    Energy.gov [DOE]

    A “Zika Virus Disease and Prevention” presentation was made by Bonnie S. Richter, MPH, PhD, at the May 19 Office of Environment, Health, Safety and Security (EHSS) All Hands Meeting.

  10. Forecasting the flu in New Mexico

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    he introduction in 1992 of an American-made truck with a fully factory-installed/war- ranted liquefied petroleum gas (LPG) engine represents another "Ford first" in the alternative fuel arena. Now the company has introduced an LPG- powered F-700, a medium/heavy- duty truck. According to Tom Steckel, Ford's medium-duty marketing man- ager, Ford's latest sales figures already prove the alternative fuel F-700's popularity. With a little more than 10 months of the model year finished, Ford

  11. Battling bird flu by the numbers

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    and crisis managers determine in real time whether an emerging infectious disease ... and crisis managers determine in real time whether an emerging infectious disease ...

  12. Toward Design of a Universal Flu Vaccine

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    ... Researchers from the Crucell Vaccine Institute in the Netherlands, using human cells from ... Friesen (Crucell Vaccine Institute, Netherlands); and O.T.W. Li, L.L.M. Poon, and M. ...

  13. From biofuels to predicting the flu

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    In addition to examples of algae growing on petri dishes and in solution, ping pong balls will help demonstrate how scientists modify the DNA of the individual cells to make them ...

  14. Better predicting flu outbreaks with Wikipedia

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Del Valle said. Del Valle and her team recently published "Forecasting the 2013-2014 Influenza Season using Wikipedia," in the Public Library of Science. "Infectious diseases are...

  15. OSTIblog Articles in the carbon capture Topic | OSTI, US Dept...

    Office of Scientific and Technical Information (OSTI)

    played a key role in building the world's first atomic bomb. It's the place where vitamin E and K were discovered, the human polio virus isolated, and the flu virus identified. ...

  16. OSTI, US Dept of Energy Office of Scientific and Technical Information...

    Office of Scientific and Technical Information (OSTI)

    played a key role in building the world's first atomic bomb. It's the place where vitamin E and K were discovered, the human polio virus isolated, and the flu virus identified. ...

  17. OSTIblog Articles in the Biofuels Topic | OSTI, US Dept of Energy...

    Office of Scientific and Technical Information (OSTI)

    played a key role in building the world's first atomic bomb. It's the place where vitamin E and K were discovered, the human polio virus isolated, and the flu virus identified. ...

  18. OSTIblog Articles in the UC Berkeley Topic | OSTI, US Dept of...

    Office of Scientific and Technical Information (OSTI)

    played a key role in building the world's first atomic bomb. It's the place where vitamin E and K were discovered, the human polio virus isolated, and the flu virus identified. ...

  19. OSTIblog Articles in the biotechnology Topic | OSTI, US Dept...

    Office of Scientific and Technical Information (OSTI)

    played a key role in building the world's first atomic bomb. It's the place where vitamin E and K were discovered, the human polio virus isolated, and the flu virus identified. ...

  20. OSTIblog Articles in the carbon sequestration Topic | OSTI, US...

    Office of Scientific and Technical Information (OSTI)

    ... played a key role in building the world's first atomic bomb. It's the place where vitamin E and K were discovered, the human polio virus isolated, and the flu virus identified. ...

  1. Conformational changes in Sindbis virus induced by decreased...

    Office of Scientific and Technical Information (OSTI)

    Sindbis virus induced by decreased pH revealed by small-angle neutron scattering Citation Details In-Document Search Title: Conformational changes in Sindbis virus induced by ...

  2. Treatment of tumors with genetically engineered herpes virus

    DOEpatents

    Weichselbaum, Ralph R; Roizman, Bernard; Whitley, Richard J

    2012-11-27

    Disclosed are methods for treating cancer by administering an effective amount of a modified Herpes simplex virus.

  3. Barley stripe mosaic virus: Structure and relationship to the tobamoviruses

    SciTech Connect

    Kendall, Amy; Williams, Dewight; Bian, Wen; Stewart, Phoebe L.; Stubbs, Gerald

    2013-09-01

    Barley stripe mosaic virus (BSMV) is the type member of the genus Hordeivirus, rigid, rod-shaped viruses in the family Virgaviridae. We have used fiber diffraction and cryo-electron microscopy to determine the helical symmetry of BSMV to be 23.2 subunits per turn of the viral helix, and to obtain a low-resolution model of the virus by helical reconstruction methods. Features in the model support a structural relationship between the coat proteins of the hordeiviruses and the tobamoviruses. - Highlights: • We report a low-resolution structure of barley stripe mosaic virus. • Barley stripe mosaic virus has 23.2 subunits per turn of the viral helix. • We compare barley stripe mosaic virus with tobacco mosaic virus.

  4. Structure of the Triatoma virus capsid

    SciTech Connect

    Squires, Gaëlle; Pous, Joan; Agirre, Jon; Rozas-Dennis, Gabriela S.; Costabel, Marcelo D.; Marti, Gerardo A.; Navaza, Jorge; Bressanelli, Stéphane; Guérin, Diego M. A.; Rey, Felix A.

    2013-06-01

    The crystallographic structure of TrV shows specific morphological and functional features that clearly distinguish it from the type species of the Cripavirus genus, CrPV. The members of the Dicistroviridae family are non-enveloped positive-sense single-stranded RNA (+ssRNA) viruses pathogenic to beneficial arthropods as well as insect pests of medical importance. Triatoma virus (TrV), a member of this family, infects several species of triatomine insects (popularly named kissing bugs), which are vectors for human trypanosomiasis, more commonly known as Chagas disease. The potential use of dicistroviruses as biological control agents has drawn considerable attention in the past decade, and several viruses of this family have been identified, with their targets covering honey bees, aphids and field crickets, among others. Here, the crystal structure of the TrV capsid at 2.5 Å resolution is reported, showing that as expected it is very similar to that of Cricket paralysis virus (CrPV). Nevertheless, a number of distinguishing structural features support the introduction of a new genus (Triatovirus; type species TrV) under the Dicistroviridae family. The most striking differences are the absence of icosahedrally ordered VP4 within the infectious particle and the presence of prominent projections that surround the fivefold axis. Furthermore, the structure identifies a second putative autoproteolytic DDF motif in protein VP3, in addition to the conserved one in VP1 which is believed to be responsible for VP0 cleavage during capsid maturation. The potential meaning of these new findings is discussed.

  5. Immobilization and One-Dimensional Arrangement of Virus Capsids with

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Nanoscale Precision Using DNA Origami Immobilization and One-Dimensional Arrangement of Virus Capsids with Nanoscale Precision Using DNA Origami Authors: Stephanopoulos, N., Liu, M., Tong, G., Li, Z., Liu, Y., Yan, H., and Francis, M. Title: Immobilization and One-Dimensional Arrangement of Virus Capsids with Nanoscale Precision Using DNA Origami Source: Nano Letters Year: 2010 Volume: 10 Pages: 2714-2720 ABSTRACT: DNA origami was used as a scaffold to arrange spherical virus capsids into

  6. Structural Rearrangement in Ebola Virus Protein VP40 Creates...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    lab revealed how the filaments undergo electrostatically driven rearrangements and polymerization to build and bud Ebola virus virions. Atomic models built from their structures...

  7. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Reveal Multiple Functions of Ebola Virus Print A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function....

  8. HIV virus spread and evolution studied through computer modeling

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    and the actual, rapid evolution of the virus (phylogenetics) within each patient's body. "We have developed novel ways of estimating epidemics dynamics such as who infected...

  9. Serial femtosecond X-ray diffraction of enveloped virus microcrystals

    SciTech Connect

    Lawrence, Robert M.; Conrad, Chelsie E.; Zatsepin, Nadia A.; Grant, Thomas D.; Liu, Haiguang; James, Daniel; Nelson, Garrett; Subramanian, Ganesh; Aquila, Andrew; Hunter, Mark S.; Liang, Mengning; Boutet, Sbastien; Coe, Jesse; Spence, John C. H.; Weierstall, Uwe; Liu, Wei; Fromme, Petra; Cherezov, Vadim; Hogue, Brenda G.

    2015-08-20

    Serial femtosecond crystallography (SFX) using X-ray free-electron lasers has produced high-resolution, room temperature, time-resolved protein structures. We report preliminary SFX of Sindbis virus, an enveloped icosahedral RNA virus with ~700 diameter. Microcrystals delivered in viscous agarose medium diffracted to ~40 resolution. Small-angle diffuse X-ray scattering overlaid Bragg peaks and analysis suggests this results from molecular transforms of individual particles. Viral proteins undergo structural changes during entry and infection, which could, in principle, be studied with SFX. This is a pertinent step toward determining room temperature structures from virus microcrystals that may enable time-resolved studies of enveloped viruses.

  10. This is a paper model of the MS2 virus

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    a paper model of the MS2 virus. MS2 is a nanoscale virus that lives in the human gut. It is benign and doesn't interfere with us. A virus, it attaches to a host cell that it identifies using protein markers on its exterior. Once attached, it injects its RNA genetic material into the cell. This material then co-opts the cell's metabolism to produce copies of the virus, which the cell releases back into the organism's tissues. Researchers have found that this mechanism has potential as a treatment

  11. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Immortality is not a ... it more rigid, essentially locking it in the correct geometry for target interactions. ...

  12. Serial femtosecond X-ray diffraction of enveloped virus microcrystals

    DOE PAGES [OSTI]

    Lawrence, Robert M.; Conrad, Chelsie E.; Zatsepin, Nadia A.; Grant, Thomas D.; Liu, Haiguang; James, Daniel; Nelson, Garrett; Subramanian, Ganesh; Aquila, Andrew; Hunter, Mark S.; et al

    2015-08-20

    Serial femtosecond crystallography (SFX) using X-ray free-electron lasers has produced high-resolution, room temperature, time-resolved protein structures. We report preliminary SFX of Sindbis virus, an enveloped icosahedral RNA virus with ~700 Å diameter. Microcrystals delivered in viscous agarose medium diffracted to ~40 Å resolution. Small-angle diffuse X-ray scattering overlaid Bragg peaks and analysis suggests this results from molecular transforms of individual particles. Viral proteins undergo structural changes during entry and infection, which could, in principle, be studied with SFX. This is a pertinent step toward determining room temperature structures from virus microcrystals that may enable time-resolved studies of enveloped viruses.

  13. Structure of the Ebola virus glycoprotein bound to an antibody...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Structure of the Ebola virus glycoprotein bound to an antibody from a human survivor ... viral surface glycoprotein in complex with a rare antibody derived from a human survivor. ...

  14. Structural Basis of Pre-existing Immunity to the 2009 H1N1 Pandemic

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Influenza Virus Structural Basis of Pre-existing Immunity to the 2009 H1N1 Pandemic Influenza Virus The emergence of the 2009 H1N1 influenza pandemic, also known as the "swine flu", marks the first human flu pandemic in 40 years and has caused significant human infection and mortality globally (1). The emergence of the 2009 H1N1 flu marks the first time that an influenza pandemic was triggered by a virus carrying the same hemagglutinin (HA) subtype as circulating seasonal strains.

  15. Tobacco mosaic virus: A biological building block for micro/nano...

    Office of Scientific and Technical Information (OSTI)

    Tobacco mosaic virus: A biological building block for micronanobio systems Citation Details In-Document Search Title: Tobacco mosaic virus: A biological building block for micro...

  16. Chimeric human parainfluenza virus bearing the Ebola virus glycoprotein as the sole surface protein is immunogenic and highly protective against Ebola virus challenge

    SciTech Connect

    Bukreyev, Alexander Marzi, Andrea; Feldmann, Friederike; Zhang Liqun; Dorward, David W.; Pickles, Raymond J.; Feldmann, Heinz; Collins, Peter L.

    2009-01-20

    We generated a new live-attenuated vaccine against Ebola virus (EBOV) based on a chimeric virus HPIV3/{delta}F-HN/EboGP that contains the EBOV glycoprotein (GP) as the sole transmembrane envelope protein combined with the internal proteins of human parainfluenza virus type 3 (HPIV3). Electron microscopy analysis of the virus particles showed that they have an envelope and surface spikes resembling those of EBOV and a particle size and shape resembling those of HPIV3. When HPIV3/{delta}F-HN/EboGP was inoculated via apical surface of an in vitro model of human ciliated airway epithelium, the virus was released from the apical surface; when applied to basolateral surface, the virus infected basolateral cells but did not spread through the tissue. Following intranasal (IN) inoculation of guinea pigs, scattered infected cells were detected in the lungs by immunohistochemistry, but infectious HPIV3/{delta}F-HN/EboGP could not be recovered from the lungs, blood, or other tissues. Despite the attenuation, the virus was highly immunogenic, and a single IN dose completely protected the animals against a highly lethal intraperitoneal challenge of guinea pig-adapted EBOV.

  17. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    SciTech Connect

    Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.; Cooper, Kurt; Jahrling, Peter B.; Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 ; Schnell, Matthias J.; Blaney, Joseph E.

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  18. OSTI News | OSTI, US Dept of Energy Office of Scientific and...

    Office of Scientific and Technical Information (OSTI)

    ... Feb 1, 2011 From the development of exotic materials to the study of flu virus shuttles, Iowa State University and DOE partnership is on the move Iowa State University's vision is ...

  19. OSTI News | OSTI, US Dept of Energy, Office of Scientific and...

    Office of Scientific and Technical Information (OSTI)

    ... Posted February 1, 2011 From the development of exotic materials to the study of flu virus shuttles, Iowa State University and DOE partnership is on the move Iowa State ...

  20. Risk of Zika virus is low in New Mexico

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Risk of Zika virus is low in New Mexico Community Connections: Your link to news and opportunities from Los Alamos National Laboratory Latest Issue:November 2, 2016 all issues All Issues » submit Risk of Zika virus is low in New Mexico Be cautious when traveling to warmer climates. June 2, 2016 Los Alamos National Lab epidemiologist Brian Foley co-authored a chapter on Zika virus in a recently published book on global virology and said there is little for New Mexicans to worry about when it

  1. Virus Assemblies as Templates for Nanocircuits

    SciTech Connect

    James N Culver; Michael T Harris

    2011-08-31

    The goals of this project were directed at the identification and characterization of bio-mineralization processes and patterning methods for the development of nano scale materials and structures with novel energy and conductive traits. This project utilized a simple plant virus as a model template to investigate methods to attach and coat metals and other inorganic compounds onto biologically based nanotemplates. Accomplishments include: the development of robust biological nanotemplates with enhanced inorganic coating activities; novel coating strategies that allow for the deposition of a continuous inorganic layer onto a bio-nanotemplate even in the absence of a reducing agent; three-dimensional patterning methods for the assemble of nano-featured high aspect ratio surfaces and the demonstrated use of these surfaces in enhancing battery and energy storage applications. Combined results from this project have significantly advanced our understanding and ability to utilize the unique self-assembly properties of biologically based molecules to produce novel materials at the nanoscale level.

  2. 1

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Fighting the flu, one cell at a time August 1, 2016 Fighting the flu, one cell at a time Fluorescent microscopy images taken at Los Alamos National Laboratory dramatize the battleground where the ion channel M2 protein of influenza virus A, labeled with a green fluorescent antibody, attacks the cellular defense protein Beclin-1, labeled with red. (The human cell nucleus is shown in blue.) The influenza A virus causes seasonal epidemics nearly ever winter in the United States. Although biologists

  3. Nanomachines: How Viruses Work, and How We Can Stop Them

    ScienceCinema

    Carolyn Bertozzi

    2016-07-12

    Nature's Nasty Nanomachines: How Viruses Work, and How We Can Stop Them. Carolyn Bertozzi, director of Berkeley Lab's Molecular Foundry, discusses this topic at a Feb. 21, 2009 Nano*High talk.

  4. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Functions of Ebola Virus Print Friday, 13 June 2014 10:25 A central dogma of molecular biology is that a protein's sequence dictates its fold, and the fold dictates its function....

  5. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called...

  6. Multidisciplinary team aids understanding of Hepatitis C virus...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    this drug could cause such a rapid drop in the amount of virus in an infected person's blood could greatly enhance the ability to design optimal drug therapies and ultimately cure...

  7. High molecular weight polysaccharide that binds and inhibits virus

    DOEpatents

    Konowalchuk, Thomas W

    2014-01-14

    This invention provides a high molecular weight polysaccharide capable of binding to and inhibiting virus and related pharmaceutical formulations and methods on inhibiting viral infectivity and/or pathogenicity, as well as immunogenic compositions. The invention further methods of inhibiting the growth of cancer cells and of ameliorating a symptom of aging. Additionally, the invention provides methods of detecting and/or quantifying and/or isolating viruses.

  8. Dengue Virus Infection Perturbs Lipid Homeostasis in Infected Mosquito Cells

    SciTech Connect

    Perera, Rushika M.; Riley, Catherine; Isaac, Georgis; Hopf- Jannasch, Amber; Moore, Ronald J.; Weitz, Karl K.; Pasa-Tolic, Ljiljana; Metz, Thomas O.; Adamec, Jiri; Kuhn, Richard J.

    2012-03-22

    Dengue virus causes {approx}50-100 million infections per year and thus is considered one of the most aggressive arthropod-borne human pathogen worldwide. During its replication, dengue virus induces dramatic alterations in the intracellular membranes of infected cells. This phenomenon is observed both in human and vector-derived cells. Using high-resolution mass spectrometry of mosquito cells, we show that this membrane remodeling is directly linked to a unique lipid repertoire induced by dengue virus infection. Specifically, 15% of the metabolites detected were significantly different between DENV infected and uninfected cells while 85% of the metabolites detected were significantly different in isolated replication complex membranes. Furthermore, we demonstrate that intracellular lipid redistribution induced by the inhibition of fatty acid synthase, the rate-limiting enzyme in lipid biosynthesis, is sufficient for cell survival but is inhibitory to dengue virus replication. Lipids that have the capacity to destabilize and change the curvature of membranes as well as lipids that change the permeability of membranes are enriched in dengue virus infected cells. Several sphingolipids and other bioactive signaling molecules that are involved in controlling membrane fusion, fission, and trafficking as well as molecules that influence cytoskeletal reorganization are also up regulated during dengue infection. These observations shed light on the emerging role of lipids in shaping the membrane and protein environments during viral infections and suggest membrane-organizing principles that may influence virus-induced intracellular membrane architecture.

  9. Enteric viruses in a mangrove lagoon, survival and shellfish incidence

    SciTech Connect

    Lopez de Cardona, I.; Bermudez, M.; Billmire, E.; Hazen, T.C.

    1988-12-31

    Mangrove oysters (Crassostrea rhizophorae) were screened for enteric viruses. For 18 months oysters were collected from Cano Boqueron, a tropical mangrove lagoon on the southwest coast of Puerto Rico. This popular tourist resort has two primary sewage treatment plants which service 158 single family cabanas. In spite of the heavy seasonal input of sewage to Cano Boqueron and high densities of fecal coliform bacteria, enteric viruses were not detected in shellfish meat. Because no viruses were detected in the oysters, a virus survival study was performed. Poliovirus type 1 was placed in diffusion chambers in situ at two sites in Cano Boqueron. More than 95% of the poliovirus inactivation occurred within 24 h. Virus inactivation was significantly different by site, indicating different inactivation rates within the lagoon. Chamber studies done simultaneously with Escherichia coli did not reveal differences between sites. It is suggested that the sewage effluent had an antiviral effect in the absence of an antibacterial effect. This study demonstrates the importance for establishing microbial contamination standards for shellfish growing waters in the tropics based upon in situ studies with tropical species, e.g. mangrove oyster.

  10. Antibody Recognition of the Pandemic H1N1 Influenza Virus Hemagglutini...

    Office of Scientific and Technical Information (OSTI)

    H1N1 Influenza Virus Hemagglutinin Receptor Binding Site Citation Details In-Document Search Title: Antibody Recognition of the Pandemic H1N1 Influenza Virus Hemagglutinin ...

  11. Engineering Paper-Based Sensors for Zika Virus

    DOE PAGES [OSTI]

    Meagher, Robert J.; Negrete, Oscar A.; Van Rompay, Koen K.

    2016-05-30

    The emergence of Zika virus in Latin America has created an urgent need for new, simple yet sensitive diagnostic tests. We highlight recent work using paper-based sensors coupled with CRISPR/Cas9 to detect Zika RNA, as a new approach to rapid development and deployment of field-ready diagnostics for emerging infectious diseases.

  12. Structure and Receptor Specificity of an Avian Flu Antigen

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    ... Publication about this research: J. Stevens, O. Blixt, T.M. Tumpey, J.K. Taubenberger, J.C. Paulson, and I.A. Wilson, "Structure and receptor specificity of the hemagglutinin from ...

  13. FLU5A425 | netl.doe.gov

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    ... bearing deep marine sediments form the Peru Margin (ODP Leg 201) and the Cascadia Margin (ODP Leg 204): American Geophysical Union, Fall Meeting, San Francisco, CA, December. ...

  14. Science on the Hill: The forecast calls for flu

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    It too is marked by huge unknowns but has steadily improved over the last half century. We expect an accurate weather report to tell us whether we should wear a heavy coat or put ...

  15. Pandemic Flu Planning | Y-12 National Security Complex

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    on employee safety and communications. History of pandemics In 1918 and 1919, an Influenza Pandemic occurred in three waves in the United States. Learn more. Resources you can...

  16. ORISE: Pandemic Flu Toolkits | How ORISE is Making a Difference

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    workshops that have been presented to the Asia-Pacific Economic Cooperation (APEC) and other nations around the world. By developing training toolkits and providing...

  17. The vaccinia virus E6 protein influences virion protein localization during virus assembly

    SciTech Connect

    Condit, Richard C. Moussatche, Nissin

    2015-08-15

    Vaccinia virus mutants in which expression of the virion core protein gene E6R is repressed are defective in virion morphogenesis. E6 deficient infections fail to properly package viroplasm into viral membranes, resulting in an accumulation of empty immature virions and large aggregates of viroplasm. We have used immunogold electron microscopy and immunofluorescence confocal microscopy to assess the intracellular localization of several virion structural proteins and enzymes during E6R mutant infections. We find that during E6R mutant infections virion membrane proteins and virion transcription enzymes maintain a normal localization within viral factories while several major core and lateral body proteins accumulate in aggregated virosomes. The results support a model in which vaccinia virions are assembled from at least three substructures, the membrane, the viroplasm and a “pre-nucleocapsid”, and that the E6 protein is essential for maintaining proper localization of the seven-protein complex and the viroplasm during assembly. - Highlights: • Mutation of E6 disrupts association of viral membranes with viral core proteins • Mutation of E6 does not perturb viral membrane biosynthesis • Mutation of E6 does not perturb localization of viral transcription enzymes • Mutation of E6 causes mis-localization and aggregation of viral core proteins • Vaccinia assembly uses three subassemblies: membranes, viroplasm, prenucleocapsid.

  18. Development of simulation tools for virus shell assembly. Final report

    SciTech Connect

    Berger, Bonnie

    2001-01-05

    Prof. Berger's major areas of research have been in applying computational and mathematical techniques to problems in biology, and more specifically to problems in protein folding and genomics. Significant progress has been made in the following areas relating to virus shell assembly: development has been progressing on a second-generation self-assembly simulator which provides a more versatile and physically realistic model of assembly; simulations are being developed and applied to a variety of problems in virus assembly; and collaborative efforts have continued with experimental biologists to verify and inspire the local rules theory and the simulator. The group has also worked on applications of the techniques developed here to other self-assembling structures in the material and biological sciences. Some of this work has been conducted in conjunction with Dr. Sorin Istrail when he was at Sandia National Labs.

  19. Structural Rearrangement in Ebola Virus Protein VP40 Creates Multiple

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Functions | Stanford Synchrotron Radiation Lightsource Structural Rearrangement in Ebola Virus Protein VP40 Creates Multiple Functions Monday, March 31, 2014 Figure 1. Three structures of VP40. Top, a butterfly-shaped dimer structure critical for membrane trafficking. Middle, a rearranged hexameric structure essential for building and releasing nascent virions. Bottom, an RNA-binding octameric ring that controls transcription in infected cells. As x-ray crystallographers, we often assume

  20. HIV virus spread and evolution studied through computer modeling

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    HIV and evolution studied through computer modeling HIV virus spread and evolution studied through computer modeling This approach distinguishes between susceptible and infected individuals to capture the full infection history, including contact tracing data for infected individuals. November 19, 2013 Scanning electron micrograph of HIV-1 budding (in green) from cultured lymphocytes. The image has been colored to highlight important features. Scanning electron micrograph of HIV-1 budding (in

  1. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    DOE PAGES [OSTI]

    Zivcec, Marko; Scholte, Florine; Spiropoulou, Christina; Spengler, Jessica; Bergeron, Éric

    2016-04-21

    Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen that causes high morbidity and mortality. Efficacy of vaccines and antivirals to treat human CCHFV infections remains limited and controversial. Research into pathology and underlying molecular mechanisms of CCHFV and other nairoviruses is limited. Significant progress has been made in our understanding of CCHFV replication and pathogenesis in the past decade. Here we review the most recent molecular advances in CCHFV-related research, and provide perspectives on future research.

  2. Adaptive evolution of simian immunodeficiency viruses isolated from two conventional progressor macaques with neuroaids

    SciTech Connect

    Foley, Brian T; Korber, Bette T

    2008-01-01

    Simian immunodeficiency virus infection of macaques may result in neuroAIDS, a feature more commonly observed in macaques with rapid progressive disease than in those with conventional disease. This is the first report of two conventional progressors (H631 and H636) with encephalitis in rhesus macaques inoculated with a derivative of SIVsmES43-3. Phylogenetic analyses of viruses isolated from the cerebral spinal fluid (CSF) and plasma from both animals demonstrated tissue compartmentalization. Additionally, virus from the central nervous system (CNS) was able to infect primary macaque monocyte-derived macrophages more efficiently than virus from plasma. Conversely, virus isolated from plasma was able to replicate better in peripheral blood mononuclear cells than virus from CNS. We speculate that these viruses were under different selective pressures in their separate compartments. Furthermore, these viruses appear to have undergone adaptive evolution to preferentially replicate in their respective cell targets. Analysis of the number of potential N-linked glycosylation sites (PNGS) in gp160 showed that there was a statistically significant loss of PNGS in viruses isolated from CNS in both macaques compared to SIVsmE543-3. Moreover, virus isolated from the brain in H631, had statistically significant loss of PNGS compared to virus isolated from CSF and plasma of the same animal. It is possible that the brain isolate may have adapted to decrease the number of PNGS given that humoral immune selection pressure is less likely to be encountered in the brain. These viruses provide a relevant model to study the adaptations required for SIV to induce encephalitis.

  3. Using X-Rays to Zap the Zika Virus | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) (indexed site)

    Using X-Rays to Zap the Zika Virus Using X-Rays to Zap the Zika Virus July 29, 2016 - 2:55pm Addthis New knowledge about the Zika Virus gets us closer to finding effective treatment. | Video by Argonne National Laboratory. Pat Adams Pat Adams Digital Content Specialist, Office of Public Affairs The Zika virus is a growing public health crisis. We don't yet have a vaccine or drug treatment to combat the spreading problem, but a team of researchers just got a big step closer. Researchers from the

  4. West Nile virus isolated from Virginia opossum (Didelphis virginiana) in Northwest Missouri 2012

    DOE PAGES [OSTI]

    Bosco-Lauth, Angela; Harmon, Jessica; Lash, R. Ryan; Weiss, Sonja; Langevin, Stanley; Savage, Harry; Marvin S. Godsey, Jr.; Burkhalter, Kristen; Root, J. Jeffrey; Gidlewski, Thomas; et al

    2014-12-01

    We describe the isolation of West Nile virus (WNV; Flaviviridae, flavivirus) from blood of a Virginia opossum (Didelphis virginiana) collected in northwestern Missouri, USA in August 2012. Furthermore, sequencing determined that the virus was related to lineage 1a WNV02 strains. We discuss the role of wildlife in WNV disease epidemiology.

  5. Venezuelan equine encephalitis virus entry mechanism requires late endosome formation and resists cell membrane cholesterol depletion

    SciTech Connect

    Kolokoltsov, Andrey A.; Fleming, Elisa H.; Davey, Robert A. . E-mail: radavey@utmb.edu

    2006-04-10

    Virus envelope proteins determine receptor utilization and host range. The choice of receptor not only permits specific targeting of cells that express it, but also directs the virus into specific endosomal trafficking pathways. Disrupting trafficking can result in loss of virus infectivity due to redirection of virions to non-productive pathways. Identification of the pathway or pathways used by a virus is, thus, important in understanding virus pathogenesis mechanisms and for developing new treatment strategies. Most of our understanding of alphavirus entry has focused on the Old World alphaviruses, such as Sindbis and Semliki Forest virus. In comparison, very little is known about the entry route taken by more pathogenic New World alphaviruses. Here, we use a novel contents mixing assay to identify the cellular requirements for entry of a New World alphavirus, Venezuelan equine encephalitis virus (VEEV). Expression of dominant negative forms of key endosomal trafficking genes shows that VEEV must access clathrin-dependent endocytic vesicles for membrane fusion to occur. Unexpectedly, the exit point is different from Old World alphaviruses that leave from early endosomes. Instead, VEEV also requires functional late endosomes. Furthermore, unlike the Old World viruses, VEEV entry is insensitive to cholesterol sequestration from cell membranes and may reflect a need to access an endocytic compartment that lacks cholesterol. This indicates fundamental differences in the entry route taken by VEEV compared to Old World alphaviruses.

  6. Inhibition of lytic infection of pseudorabies virus by arginine depletion

    SciTech Connect

    Wang, H.-C. [Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan (China); Kao, Y.-C. [Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan (China); Chang, T-J. [Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan (China); Wong, M.-L. [Department of Veterinary Medicine, College of Veterinary Medicine, National Chung-Hsing University, Taichung 402, Taiwan (China)]. E-mail: mlwong@dragon.nchu.edu.tw

    2005-08-26

    Pseudorabies virus (PRV) is a member of Alphahepesviruses; it is an enveloped virus with a double-stranded DNA genome. Polyamines (such as spermine and spermidine) are ubiquitous in animal cells and participate in cellular proliferation and differentiation. Previous results of our laboratory showed that the PRV can accomplish lytic infection either in the presence of exogenous spermine (or spermidine) or depletion of cellular polyamines. The amino acid arginine is a precursor of polyamine biosynthesis. In this work, we investigated the role of arginine in PRV infection. It was found that the plaque formation of PRV was inhibited by arginase (enzyme catalyzing the conversion of arginine into ornithine and urea) treatment whereas this inhibition can be reversed by exogenous arginine, suggesting that arginine is essential for PRV proliferation. Western blotting was conducted to study the effect of arginine depletion on the levels of structural proteins of PRV in virus-infected cells. Four PRV structural proteins (gB, gE, UL47, and UL48) were chosen for examination, and results revealed that the levels of viral proteins were obviously reduced in long time arginase treatment. However, the overall protein synthesis machinery was apparently not influenced by arginase treatment either in mock or PRV-infected cells. Analyzing with native gel, we found that arginase treatment affected the mobility of PRV structural proteins, suggesting the conformational change of viral proteins by arginine depletion. Heat shock proteins, acting as molecular chaperons, participate in protein folding and translocation. Our results demonstrated that long time arginase treatment could reduce the expression of cellular heat shock proteins 70 (hsc70 and hsp70), and transcriptional suppression of heat shock protein 70 gene promoter was one of the mechanisms involved in this reduced expression.

  7. LINGUISTIC ANALYSIS OF THE NUCLEOPROTEIN GENE OF INFLUENZA A VIRUS

    SciTech Connect

    A. SKOURIKHINE; T. BURR

    2000-05-01

    We applied linguistic analysis approach, specifically N-grams, to classify nucleotide and amino acids sequences of nucleoprotein (NP) gene of the Influenza A virus isolated from a range of hosts and geographic regions. We considered letter frequency (1-grams), letter pairs frequency (2-grams) and triplets' frequency (3-grams). Classification trees based on 1,2,3-grams variables were constructed for the same NP nucleotide and amino acids strains and their classification efficiency were compared with the clustering obtained using phylogenetic analysis. The results have shown that disregarding positional information for a NP gene can provide the same level of recognition accuracy like alternative more complex classification techniques.

  8. The V domain of dog PVRL4 (nectin-4) mediates canine distemper virus entry and virus cell-to-cell spread

    SciTech Connect

    Delpeut, Sebastien; Noyce, Ryan S.; Richardson, Christopher D.

    2014-04-15

    The entry of canine distemper virus (CDV) is a multistep process that involves the attachment of CDV hemagglutinin (H) to its cellular receptor, followed by fusion between virus and cell membranes. Our laboratory recently identified PVRL4 (nectin-4) to be the epithelial receptor for measles and canine distemper viruses. In this study, we demonstrate that the V domain of PVRL4 is critical for CDV entry and virus cell-to-cell spread. Furthermore, four key amino acid residues within the V domain of dog PVRL4 and two within the CDV hemagglutinin were shown to be essential for receptor-mediated virus entry. - Highlights: • PVRL4 (nectin-4) is the epithelial cell receptor for measles and canine distemper viruses. • V domain of PVRL4 is critical for CDV entry, cell-to-cell spread, and syncytia formation. • Chimeric PVRL1 backbone substituted with the V domain of PVRL4 can function as a receptor. • Amino acids (F132/P133/A134/G135) within the V domain are essential for PVRL4 receptor activity. • Amino acids (P493/Y539) within CDV H protein are essential for PVRL4 receptor interaction.

  9. Crystal structures of the reverse transcriptase-associated ribonuclease H domain of xenotropic murine leukemia-virus related virus

    SciTech Connect

    Zhou, Dongwen; Chung, Suhman; Miller, Maria; Le Grice, Stuart F.J.; Wlodawer, Alexander

    2012-06-19

    The ribonuclease H (RNase H) domain of retroviral reverse transcriptase (RT) plays a critical role in the life cycle by degrading the RNA strands of DNA/RNA hybrids. In addition, RNase H activity is required to precisely remove the RNA primers from nascent (-) and (+) strand DNA. We report here three crystal structures of the RNase H domain of xenotropic murine leukemia virus-related virus (XMRV) RT, namely (i) the previously identified construct from which helix C was deleted, (ii) the intact domain, and (iii) the intact domain complexed with an active site {alpha}-hydroxytropolone inhibitor. Enzymatic assays showed that the intact RNase H domain retained catalytic activity, whereas the variant lacking helix C was only marginally active, corroborating the importance of this helix for enzymatic activity. Modeling of the enzyme-substrate complex elucidated the essential role of helix C in binding a DNA/RNA hybrid and its likely mode of recognition. The crystal structure of the RNase H domain complexed with {beta}-thujaplicinol clearly showed that coordination by two divalent cations mediates recognition of the inhibitor.

  10. Non-coding RNAs and heme oxygenase-1 in vaccinia virus infection

    SciTech Connect

    Meseda, Clement A.; Srinivasan, Kumar; Wise, Jasen; Catalano, Jennifer; Yamada, Kenneth M.; Dhawan, Subhash

    2014-11-07

    Highlights: Heme oxygenase-1 (HO-1) induction inhibited vaccinia virus infection of macrophages. Reduced infectivity inversely correlated with increased expression of non-coding RNAs. The regulation of HO-1 and ncRNAs suggests a novel host defense response against vaccinia virus infection. - Abstract: Small nuclear RNAs (snRNAs) are <200 nucleotide non-coding uridylate-rich RNAs. Although the functions of many snRNAs remain undetermined, a population of snRNAs is produced during the early phase of infection of cells by vaccinia virus. In the present study, we demonstrate a direct correlation between expression of the cytoprotective enzyme heme oxygenase-1 (HO-1), suppression of selective snRNA expression, and inhibition of vaccinia virus infection of macrophages. Hemin induced HO-1 expression, completely reversed virus-induced host snRNA expression, and suppressed vaccinia virus infection. This involvement of specific virus-induced snRNAs and associated gene clusters suggests a novel HO-1-dependent host-defense pathway in poxvirus infection.

  11. Isolation and characterization of Solenopsis invicta virus 3, a new positive-strand RNA virus infecting the red imported fire ant, Solenopsis invicta

    SciTech Connect

    Valles, Steven M.; Hashimoto, Yoshifumi

    2009-06-05

    We report the discovery of a new virus from the red imported fire ant, Solenopsis invicta. Solenopsis invicta virus 3 (SINV-3) represents the third virus discovered from this ant species using the metagenomics approach. The single (positive)-strand RNA, monopartite, bicistronic genome of SINV-3 was sequenced in entirety (GenBank accession number (FJ528584)), comprised of 10,386 nucleotides, and polyadenylated at the 3' terminus. This genome size was confirmed by Northern analysis. The genome revealed 2 large open reading frames (ORFs) in the sense orientation with an untranslated region (UTR) at each end and between the two ORFs. The 5' proximal ORF (ORF 1) encoded a predicted protein of 299.1 kDa (2580 amino acids). The 3' proximal ORF (ORF 2) encoded a predicted protein of 73.2 kDa (651 amino acids). RNA-dependent RNA polymerase (RdRp), helicase, and protease domains were recognized in ORF 1. SDS-PAGE separation of purified SINV-3 particles yielded 2 bands (ostensibly capsid proteins) with a combined molecular mass of 77.3 kDa which was similar to the mass predicted by ORF 2 (73.2 kDa). Phylogenetic analysis of the conserved amino acid sequences containing domains I to VIII of the RdRp from dicistroviruses, iflaviruses, plant small RNA viruses, picornaviruses, and 4 unassigned positive-strand RNA viruses revealed a trichotomous phenogram with SINV-3 and Kelp fly virus comprising a unique cluster. Electron microscopic examination of negatively stained samples of SINV-3 revealed isometric particles with apparent projections and a diameter of 27.3 +- 1.3 nm. SINV-3 was successfully transmitted to uninfected workers by feeding. The minus (replicative) strand of SINV-3 was detected in worker ants indicating replication of the virus. The possibility of using SINV-3 as a microbial control agent for fire ants is discussed.

  12. Genomics-enabled sensor platform for rapid detection of viruses related to

    Office of Scientific and Technical Information (OSTI)

    disease outbreak. (Technical Report) | SciTech Connect Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Citation Details In-Document Search Title: Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak. Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the

  13. Human monoclonal antibodies derived from a patient infected with 2009 pandemic influenza A virus broadly cross-neutralize group 1 influenza viruses

    SciTech Connect

    Pan, Yang; Sasaki, Tadahiro; Du, Anariwa; and others

    2014-07-18

    Highlights: Influenza infection can elicit heterosubtypic antibodies to group 1 influenza virus. Three human monoclonal antibodies were generated from an H1N1-infected patient. The antibodies predominantly recognized ?-helical stem of viral hemagglutinin (HA). The antibodies inhibited HA structural activation during the fusion process. The antibodies are potential candidates for future antibody therapy to influenza. - Abstract: Influenza viruses are a continuous threat to human public health because of their ability to evolve rapidly through genetic drift and reassortment. Three human monoclonal antibodies (HuMAbs) were generated in this study, 1H11, 2H5 and 5G2, and they cross-neutralize a diverse range of group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H5N1 and H9N2. The three HuMAbs were prepared by fusing peripheral blood lymphocytes from an H1N1pdm-infected patient with a newly developed fusion partner cell line, SPYMEG. All the HuMAbs had little hemagglutination inhibition activity but had strong membrane-fusion inhibition activity against influenza viruses. A protease digestion assay showed the HuMAbs targeted commonly a short ?-helix region in the stalk of the hemagglutinin. Furthermore, Ile45Phe and Glu47Gly double substitutions in the ?-helix region made the HA unrecognizable by the HuMAbs. These two amino acid residues are highly conserved in the HAs of H1N1, H5N1 and H9N2 viruses. The HuMAbs reported here may be potential candidates for the development of therapeutic antibodies against group 1 influenza viruses.

  14. Chimeric SV40 virus-like particles induce specific cytotoxicity and protective immunity against influenza A virus without the need of adjuvants

    SciTech Connect

    Kawano, Masaaki; Morikawa, Katsuma; Suda, Tatsuya; Ohno, Naohito; Matsushita, Sho; Akatsuka, Toshitaka; Handa, Hiroshi; Matsui, Masanori

    2014-01-05

    Virus-like particles (VLPs) are a promising vaccine platform due to the safety and efficiency. However, it is still unclear whether polyomavirus-based VLPs are useful for this purpose. Here, we attempted to evaluate the potential of polyomavirus VLPs for the antiviral vaccine using simian virus 40 (SV40). We constructed chimeric SV40-VLPs carrying an HLA-A{sup ⁎}02:01-restricted, cytotoxic T lymphocyte (CTL) epitope derived from influenza A virus. HLA-A{sup ⁎}02:01-transgenic mice were then immunized with the chimeric SV40-VLPs. The chimeric SV40-VLPs effectively induced influenza-specific CTLs and heterosubtypic protection against influenza A viruses without the need of adjuvants. Because DNase I treatment of the chimeric SV40-VLPs did not disrupt CTL induction, the intrinsic adjuvant property may not result from DNA contaminants in the VLP preparation. In addition, immunization with the chimeric SV40-VLPs generated long-lasting memory CTLs. We here propose that the chimeric SV40-VLPs harboring an epitope may be a promising CTL-based vaccine platform with self-adjuvant properties. - Highlights: • We constructed chimeric SV40-VLPs carrying an influenza virus-derived CTL epitope. • Chimeric SV40-VLPs induce influenza-specific CTLs in mice without adjuvants. • Chimeric SV40-VLPs induce heterosubtypic protection against influenza A viruses. • Chimeric SV40-VLPs induce long-lasting memory CTLs. • Chimeric SV40-VLPs is a promising vaccine platform with self-adjuvant properties.

  15. Complete inactivation of Venezuelan equine encephalitis virus by 1,5-iodonaphthylazide

    SciTech Connect

    Sharma, Anuj; Raviv, Yossef; Puri, Anu; Viard, Mathias; Blumenthal, Robert; Maheshwari, Radha K. . E-mail: rmaheshwari@usuhs.mil

    2007-06-29

    Hydrophobic alkylating compounds like 1,5-iodonaphthylazide (INA) partitions into biological membranes and accumulates selectively into the hydrophobic domain of the lipid bilayer. Upon irradiation with far UV light, INA binds selectively to transmembrane proteins in the viral envelope and renders them inactive. Such inactivation does not alter the ectodomains of the membrane proteins thus preserving the structural and conformational integrity of immunogens on the surface of the virus. In this study, we have used INA to inactivate Venezuelan equine encephalitis virus (VEEV). Treatment of VEEV with INA followed by irradiation with UV light resulted in complete inactivation of the virus. Immuno-fluorescence for VEEV and virus titration showed no virus replication in-vitro. Complete loss of infectivity was also achieved in mice infected with INA treated plus irradiated preparations of VEEV. No change in the structural integrity of VEEV particles were observed after treatment with INA plus irradiation as assessed by electron microscopy. This data suggest that such inactivation strategies can be used for developing vaccine candidates for VEEV and other enveloped viruses.

  16. Structural basis for the antibody neutralization of Herpes simplex virus

    SciTech Connect

    Lee, Cheng-Chung; Lin, Li-Ling; Chan, Woan-Eng; Ko, Tzu-Ping; Lai, Jiann-Shiun; Wang, Andrew H.-J.

    2013-10-01

    The gD–E317-Fab complex crystal revealed the conformational epitope of human mAb E317 on HSV gD, providing a molecular basis for understanding the viral neutralization mechanism. Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor, which is required to trigger membrane fusion for virion entry into the host cell. gD has become a validated anti-HSV target for therapeutic antibody development. The highly inhibitory human monoclonal antibody E317 (mAb E317) was previously raised against HSV gD for viral neutralization. To understand the structural basis of antibody neutralization, crystals of the gD ectodomain bound to the E317 Fab domain were obtained. The structure of the complex reveals that E317 interacts with gD mainly through the heavy chain, which covers a large area for epitope recognition on gD, with a flexible N-terminal and C-terminal conformation. The epitope core structure maps to the external surface of gD, corresponding to the binding sites of two receptors, herpesvirus entry mediator (HVEM) and nectin-1, which mediate HSV infection. E317 directly recognizes the gD–nectin-1 interface and occludes the HVEM contact site of gD to block its binding to either receptor. The binding of E317 to gD also prohibits the formation of the N-terminal hairpin of gD for HVEM recognition. The major E317-binding site on gD overlaps with either the nectin-1-binding residues or the neutralizing antigenic sites identified thus far (Tyr38, Asp215, Arg222 and Phe223). The epitopes of gD for E317 binding are highly conserved between two types of human herpesvirus (HSV-1 and HSV-2). This study enables the virus-neutralizing epitopes to be correlated with the receptor-binding regions. The results further strengthen the previously demonstrated therapeutic and diagnostic potential of the E317 antibody.

  17. Virus and Bacterial Cell Chemical Analysis by NanoSIMS

    SciTech Connect

    Weber, P; Holt, J

    2008-07-28

    In past work for the Department of Homeland Security, the LLNL NanoSIMS team has succeeded in extracting quantitative elemental composition at sub-micron resolution from bacterial spores using nanometer-scale secondary ion mass spectrometry (NanoSIMS). The purpose of this task is to test our NanoSIMS capabilities on viruses and bacterial cells. This initial work has proven successful. We imaged Tobacco Mosaic Virus (TMV) and Bacillus anthracis Sterne cells using scanning electron microscopy (SEM) and then analyzed those samples by NanoSIMS. We were able resolve individual viral particles ({approx}18 nm by 300 nm) in the SEM and extract correlated elemental composition in the NanoSIMS. The phosphorous/carbon ratio observed in TMV is comparable to that seen in bacterial spores (0.033), as was the chlorine/carbon ratio (0.11). TMV elemental composition is consistent from spot to spot, and TMV is readily distinguished from debris by NanoSIMS analysis. Bacterial cells were readily identified in the SEM and relocated in the NanoSIMS for elemental analysis. The Ba Sterne cells were observed to have a measurably lower phosphorous/carbon ratio (0.005), as compared to the spores produced in the same run (0.02). The chlorine/carbon ratio was approximately 2.5X larger in the cells (0.2) versus the spores (0.08), while the fluorine/carbon ratio was approximately 10X lower in the cells (0.008) than the spores (0.08). Silicon/carbon ratios for both cells and spores encompassed a comparable range. The initial data in this study suggest that high resolution analysis is useful because it allows the target agent to be analyzed separate from particulates and other debris. High resolution analysis would also be useful for trace sample analysis. The next step in this work is to determine the potential utility of elemental signatures in these kinds of samples. We recommend bulk analyses of media and agent samples to determine the range of media compositions in use, and to determine how

  18. Evolution of canine and equine influenza (H3N8) viruses co-circulating between 2005 and 2008

    SciTech Connect

    Rivailler, Pierre; Perry, Ijeoma A.; Jang Yunho; Davis, C. Todd; Chen Limei; Dubovi, Edward J.; Donis, Ruben O.

    2010-12-05

    Influenza virus, subtype H3N8, was transmitted from horses to greyhound dogs in 2004 and subsequently spread to pet dog populations. The co-circulation of H3N8 viruses in dogs and horses makes bi-directional virus transmission between these animal species possible. To understand the dynamics of viral transmission, we performed virologic surveillance in dogs and horses between 2005 and 2008 in the United States. The genomes of influenza A H3N8 viruses isolated from 36 dogs and horses were sequenced to determine their origin and evolution. Phylogenetic analyses revealed that H3N8 influenza viruses from horses and dogs were monophyletic and distinct. There was no evidence of canine influenza virus infection in horses with respiratory disease or new introductions of equine influenza viruses into dogs in the United States. Analysis of a limited number of equine influenza viruses suggested substantial separation in the transmission of viruses causing clinically apparent influenza in dogs and horses.

  19. Inhibition of influenza virus infection and hemagglutinin cleavage by the protease inhibitor HAI-2

    SciTech Connect

    Hamilton, Brian S.; Chung, Changik; Cyphers, Soreen Y.; Rinaldi, Vera D.; Marcano, Valerie C.; Whittaker, Gary R.

    2014-07-25

    Highlights: • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza HA cleavage activation. • Biochemical and cell biological analysis of HAI-2 as an inhibitor of influenza virus infection. • Comparative analysis of HAI-2 for vesicular stomatitis virus and human parainfluenza virus type-1. • Analysis of the activity of HAI-2 in a mouse model of influenza. - Abstract: Influenza virus remains a significant concern to public health, with the continued potential for a high fatality pandemic. Vaccination and antiviral therapeutics are effective measures to circumvent influenza virus infection, however, multiple strains have emerged that are resistant to the antiviral therapeutics currently on the market. With this considered, investigation of alternative antiviral therapeutics is being conducted. One such approach is to inhibit cleavage activation of the influenza virus hemagglutinin (HA), which is an essential step in the viral replication cycle that permits viral-endosome fusion. Therefore, targeting trypsin-like, host proteases responsible for HA cleavage in vivo may prove to be an effective therapeutic. Hepatocyte growth factor activator inhibitor 2 (HAI-2) is naturally expressed in the respiratory tract and is a potent inhibitor of trypsin-like serine proteases, some of which have been determined to cleave HA. In this study, we demonstrate that HAI-2 is an effective inhibitor of cleavage of HA from the human-adapted H1 and H3 subtypes. HAI-2 inhibited influenza virus H1N1 infection in cell culture, and HAI-2 administration showed protection in a mouse model of influenza. HAI-2 has the potential to be an effective, alternative antiviral therapeutic for influenza.

  20. Adaptive immunity and histopathology in frog virus 3-infected Xenopus

    SciTech Connect

    Robert, Jacques . E-mail: robert@mail.rochester.edu; Morales, Heidi; Buck, Wayne; Cohen, Nicholas; Marr, Shauna; Gantress, Jennifer

    2005-02-20

    Xenopus has been used as an experimental model to evaluate the contribution of adaptive cellular immunity in amphibian host susceptibility to the emerging ranavirus FV3. Conventional histology and immunohistochemistry reveal that FV3 has a strong tropism for the proximal tubular epithelium of the kidney and is rarely disseminated elsewhere in Xenopus hosts unless their immune defenses are impaired or developmentally immature as in larvae. In such cases, virus is found widespread in most tissues. Adults, immunocompromised by depletion of CD8{sup +} T cells or by sub-lethal {gamma}-irradiation, show increased susceptibility to FV3 infection. Larvae and irradiated (but not normal) adults can be cross-infected through water by infected adult conspecifics (irradiated or not). The natural MHC class I deficiency and the absence of effect of anti-CD8 treatment on both larval CD8{sup +} T cells and larval susceptibility to FV3 are consistent with an inefficient CD8{sup +} T cell effector function during this developmental period.

  1. Selective Destruction Of Cells Infected With The Human Immunodeficiency Virus

    DOEpatents

    Keener, William K.; Ward, Thomas E.

    2006-03-28

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a varient of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  2. Selective destruction of cells infected with human immunodeficiency virus

    DOEpatents

    Keener, William K.; Ward, Thomas E.

    2003-09-30

    Compositions and methods for selectively killing a cell containing a viral protease are disclosed. The composition is a variant of a protein synthesis inactivating toxin wherein a viral protease cleavage site is interposed between the A and B chains. The variant of the type II ribosome-inactivating protein is activated by digestion of the viral protease cleavage site by the specific viral protease. The activated ribosome-inactivating protein then kills the cell by inactivating cellular ribosomes. A preferred embodiment of the invention is specific for human immunodeficiency virus (HIV) and uses ricin as the ribosome-inactivating protein. In another preferred embodiment of the invention, the variant of the ribosome-inactivating protein is modified by attachment of one or more hydrophobic agents. The hydrophobic agent facilitates entry of the variant of the ribosome-inactivating protein into cells and can lead to incorporation of the ribosome-inactivating protein into viral particles. Still another preferred embodiment of the invention includes a targeting moiety attached to the variants of the ribosome-inactivating protein to target the agent to HIV infectable cells.

  3. Kinetics of Coinfection with Influenza A Virus and Streptococcus pneumoniae

    DOE PAGES [OSTI]

    Smith, Amber M.; Adler, Frederick R.; Ribeiro, Ruy M.; Gutenkunst, Ryan N.; McAuley, Julie L.; McCullers, Jonathan A.; Perelson, Alan S.

    2013-03-21

    Secondary bacterial infections are a leading cause of illness and death during epidemic and pandemic influenza. Experimental studies suggest a lethal synergism between influenza and certain bacteria, particularly Streptococcus pneumoniae, but the precise processes involved are unclear. In this paper, to address the mechanisms and determine the influences of pathogen dose and strain on disease, we infected groups of mice with either the H1N1 subtype influenza A virus A/Puerto Rico/8/34 (PR8) or a version expressing the 1918 PB1-F2 protein (PR8-PB1-F2(1918)), followed seven days later with one of two S. pneumoniae strains, type 2 D39 or type 3 A66.1. We determinedmore » that, following bacterial infection, viral titers initially rebound and then decline slowly. Bacterial titers rapidly rise to high levels and remain elevated. We used a kinetic model to explore the coupled interactions and study the dominant controlling mechanisms. We hypothesize that viral titers rebound in the presence of bacteria due to enhanced viral release from infected cells, and that bacterial titers increase due to alveolar macrophage impairment. Dynamics are affected by initial bacterial dose but not by the expression of the influenza 1918 PB1-F2 protein. Finally, our model provides a framework to investigate pathogen interaction during coinfections and to uncover dynamical differences based on inoculum size and strain.« less

  4. Crystal Structure of a Virus-Encoded Putative Glycosyltransferase

    SciTech Connect

    Xiang, Ye; Baxa, Ulrich; Zhang, Ying; Steven, Alasdair C.; Lewis, Gentry L.; Van Etten, James L.; Rossmann, Michael G.

    2010-11-22

    The chloroviruses (family Phycodnaviridae), unlike most viruses, encode some, if not most, of the enzymes involved in the glycosylation of their structural proteins. Annotation of the gene product B736L from chlorovirus NY-2A suggests that it is a glycosyltransferase. The structure of the recombinantly expressed B736L protein was determined by X-ray crystallography to 2.3-{angstrom} resolution, and the protein was shown to have two nucleotide-binding folds like other glycosyltransferase type B enzymes. This is the second structure of a chlorovirus-encoded glycosyltransferase and the first structure of a chlorovirus type B enzyme to be determined. B736L is a retaining enzyme and belongs to glycosyltransferase family 4. The donor substrate was identified as GDP-mannose by isothermal titration calorimetry and was shown to bind into the cleft between the two domains in the protein. The active form of the enzyme is probably a dimer in which the active centers are separated by about 40 {angstrom}.

  5. Characterization of genetic variability of Venezuelan equine encephalitis viruses

    DOE PAGES [OSTI]

    Gardner, Shea N.; McLoughlin, Kevin; Be, Nicholas A.; Allen, Jonathan; Weaver, Scott C.; Forrester, Naomi; Guerbois, Mathilde; Jaing, Crystal

    2016-04-07

    Venezuelan equine encephalitis virus (VEEV) is a mosquito-borne alphavirus that has caused large outbreaks of severe illness in both horses and humans. New approaches are needed to rapidly infer the origin of a newly discovered VEEV strain, estimate its equine amplification and resultant epidemic potential, and predict human virulence phenotype. We performed whole genome single nucleotide polymorphism (SNP) analysis of all available VEE antigenic complex genomes, verified that a SNP-based phylogeny accurately captured the features of a phylogenetic tree based on multiple sequence alignment, and developed a high resolution genome-wide SNP microarray. We used the microarray to analyze a broadmore » panel of VEEV isolates, found excellent concordance between array- and sequence-based SNP calls, genotyped unsequenced isolates, and placed them on a phylogeny with sequenced genomes. The microarray successfully genotyped VEEV directly from tissue samples of an infected mouse, bypassing the need for viral isolation, culture and genomic sequencing. Lastly, we identified genomic variants associated with serotypes and host species, revealing a complex relationship between genotype and phenotype.« less

  6. The nucleocapsid protein of measles virus blocks host interferon response

    SciTech Connect

    Takayama, Ikuyo; Sato, Hiroki; Watanabe, Akira; Omi-Furutani, Mio; Sugai, Akihiro; Kanki, Keita; Yoneda, Misako; Kai, Chieko

    2012-03-01

    Measles virus (MV) belongs to the genus Morbillivirus of the family Paramyxoviridae. A number of paramyxoviruses inhibit host interferon (IFN) signaling pathways in host immune systems by various mechanisms. Inhibition mechanisms have been described for many paramyxoviruses. Although there are inconsistencies among previous reports concerning MV, it appears that P/V/C proteins interfere with the pathways. In this study, we confirmed the effects of MV P gene products of a wild MV strain on IFN pathways and examined that of other viral proteins on it. Interestingly, we found that N protein acts as an IFN-{alpha}/{beta} and {gamma}-antagonist as strong as P gene products. We further investigated the mechanisms of MV-N inhibition, and revealed that MV-N blocks the nuclear import of activated STAT without preventing STAT and Jak activation or STAT degradation, and that the nuclear translocation of MV-N is important for the inhibition. The inhibitory effect of the N protein was observed as a common feature of other morbilliviruses. The results presented in this report suggest that N protein of MV as well as P/V/C proteins is involved in the inhibition of host IFN signaling pathways.

  7. Alteration of cell cycle progression by Sindbis virus infection

    SciTech Connect

    Yi, Ruirong; Saito, Kengo; Isegawa, Naohisa; Shirasawa, Hiroshi

    2015-07-10

    We examined the impact of Sindbis virus (SINV) infection on cell cycle progression in a cancer cell line, HeLa, and a non-cancerous cell line, Vero. Cell cycle analyses showed that SINV infection is able to alter the cell cycle progression in both HeLa and Vero cells, but differently, especially during the early stage of infection. SINV infection affected the expression of several cell cycle regulators (CDK4, CDK6, cyclin E, p21, cyclin A and cyclin B) in HeLa cells and caused HeLa cells to accumulate in S phase during the early stage of infection. Monitoring SINV replication in HeLa and Vero cells expressing cell cycle indicators revealed that SINV which infected HeLa cells during G{sub 1} phase preferred to proliferate during S/G{sub 2} phase, and the average time interval for viral replication was significantly shorter in both HeLa and Vero cells infected during G{sub 1} phase than in cells infected during S/G{sub 2} phase. - Highlights: • SINV infection was able to alter the cell cycle progression of infected cancer cells. • SINV infection can affect the expression of cell cycle regulators. • SINV infection exhibited a preference for the timing of viral replication among the cell cycle phases.

  8. News Item

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Outsmarting Thermodynamics in Self-assembly of Nanostructures If you can uniformly break the symmetry of nanorod pairs in a colloidal solution, you're one step closer to achieving...

  9. NREL: Solar Research - News Release Archives

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    December 28, 2012 Award-Winning PV Cell Pushes Efficiency Higher NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell. ...

  10. 2012 Feature Stories | NREL

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell. Award-Winning AC Uses Old Idea, New Materials Award-Winning AC Uses ...

  11. 2012 News | Solar | NREL

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell. December 4, 2012 NREL Teams with Berkeley Lab to Analyze Solar Pricing ...

  12. 2012 News | PV | NREL

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell. December 4, 2012 NREL Teams with Berkeley Lab to Analyze Solar Pricing ...

  13. 2012 News | Awards and Honors | NREL

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    NREL and Solar Junction outsmart the solar spectrum and set a world record with a 44%-efficient solar cell. December 17, 2012 Award-Winning AC Uses Old Idea, New Materials NREL's ...

  14. P1-Substituted Symmetry-Based Human Immunodeficiency Virus Protease Inhibitors with Potent Antiviral Activity against Drug-Resistant Viruses

    SciTech Connect

    DeGoey, David A.; Grampovnik, David J.; Chen, Hui-Ju; Flosi, William J.; Klein, Larry L.; Dekhtyar, Tatyana; Stoll, Vincent; Mamo, Mulugeta; Molla, Akhteruzzaman; Kempf, Dale J.

    2013-03-07

    Because there is currently no cure for HIV infection, patients must remain on long-term drug therapy, leading to concerns over potential drug side effects and the emergence of drug resistance. For this reason, new and safe antiretroviral agents with improved potency against drug-resistant strains of HIV are needed. A series of HIV protease inhibitors (PIs) with potent activity against both wild-type (WT) virus and drug-resistant strains of HIV was designed and synthesized. The incorporation of substituents with hydrogen bond donor and acceptor groups at the P1 position of our symmetry-based inhibitor series resulted in significant potency improvements against the resistant mutants. By this approach, several compounds, such as 13, 24, and 29, were identified that demonstrated similar or improved potencies compared to 1 against highly mutated strains of HIV derived from patients who previously failed HIV PI therapy. Overall, compound 13 demonstrated the best balance of potency against drug resistant strains of HIV and oral bioavailability in pharmacokinetic studies. X-ray analysis of an HIV PI with an improved resistance profile bound to WT HIV protease is also reported.

  15. Deletions in the fifth alpha helix of HIV-1 matrix block virus release

    SciTech Connect

    Sanford, Bridget; Li, Yan; Maly, Connor J.; Madson, Christian J.; Chen, Han; Zhou, You; Belshan, Michael

    2014-11-15

    The matrix (MA) protein of HIV-1 is the N-terminal component of the Gag structural protein and is critical for the early and late stages of viral replication. MA contains five α-helices (α1–α5). Deletions in the N-terminus of α5 as small as three amino acids impaired virus release. Electron microscopy of one deletion mutant (MA∆96-120) showed that its particles were tethered to the surface of cells by membranous stalks. Immunoblots indicated all mutants were processed completely, but mutants with large deletions had alternative processing intermediates. Consistent with the EM data, MA∆96-120 retained membrane association and multimerization capability. Co-expression of this mutant inhibited wild type particle release. Alanine scanning mutation in this region did not affect virus release, although the progeny virions were poorly infectious. Combined, these data demonstrate that structural ablation of the α5 of MA inhibits virus release. - Highlights: • Deletions were identified in the C-terminus of matrix that block virus release. • These deletion mutants still multimerized and associated with membranes. • TEM showed the mutant particles were tethered to the cell surface. • Amino acid mutagenesis of the region did not affect release. • The data suggests that disruption of matrix structure blocks virus release.

  16. Actin-myosin network is required for proper assembly of influenza virus particles

    SciTech Connect

    Kumakura, Michiko; Kawaguchi, Atsushi Nagata, Kyosuke

    2015-02-15

    Actin filaments are known to play a central role in cellular dynamics. After polymerization of actin, various actin-crosslinking proteins including non-muscle myosin II facilitate the formation of spatially organized actin filament networks. The actin-myosin network is highly expanded beneath plasma membrane. The genome of influenza virus (vRNA) replicates in the cell nucleus. Then, newly synthesized vRNAs are nuclear-exported to the cytoplasm as ribonucleoprotein complexes (vRNPs), followed by transport to the beneath plasma membrane where virus particles assemble. Here, we found that, by inhibiting actin-myosin network formation, the virus titer tends to be reduced and HA viral spike protein is aggregated on the plasma membrane. These results indicate that the actin-myosin network plays an important role in the virus formation. - Highlights: • Actin-myosin network is important for the influenza virus production. • HA forms aggregations at the plasma membrane in the presence of blebbistatin. • M1 is recruited to the budding site through the actin-myosin network.

  17. West Nile virus isolated from Virginia opossum (Didelphis virginiana) in Northwest Missouri 2012

    SciTech Connect

    Bosco-Lauth, Angela; Harmon, Jessica; Lash, R. Ryan; Weiss, Sonja; Langevin, Stanley; Savage, Harry; Marvin S. Godsey, Jr.; Burkhalter, Kristen; Root, J. Jeffrey; Gidlewski, Thomas; Nicholson, William; Brault, Aaron C.; Komar, Nicholas

    2014-12-01

    We describe the isolation of West Nile virus (WNV; Flaviviridae, flavivirus) from blood of a Virginia opossum (Didelphis virginiana) collected in northwestern Missouri, USA in August 2012. Furthermore, sequencing determined that the virus was related to lineage 1a WNV02 strains. We discuss the role of wildlife in WNV disease epidemiology.

  18. Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor

    DOE PAGES [OSTI]

    Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

    2015-04-14

    Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 10⁴ PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodologymore » has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.« less

  19. Rapid detection of Ebola virus with a reagent-free, point-of-care biosensor

    SciTech Connect

    Baca, Justin T.; Severns, Virginia; Lovato, Debbie; Branch, Darren W.; Larson, Richard S.

    2015-04-14

    Surface acoustic wave (SAW) sensors can rapidly detect Ebola antigens at the point-of-care without the need for added reagents, sample processing, or specialized personnel. This preliminary study demonstrates SAW biosensor detection of the Ebola virus in a concentration-dependent manner. The detection limit with this methodology is below the average level of viremia detected on the first day of symptoms by PCR. We observe a log-linear sensor response for highly fragmented Ebola viral particles, with a detection limit corresponding to 1.9 × 10⁴ PFU/mL prior to virus inactivation. We predict greatly improved sensitivity for intact, infectious Ebola virus. This point-of-care methodology has the potential to detect Ebola viremia prior to symptom onset, greatly enabling infection control and rapid treatment. This biosensor platform is powered by disposable AA batteries and can be rapidly adapted to detect other emerging diseases in austere conditions.

  20. Three dimensional colorimetric assay assemblies

    DOEpatents

    Charych, Deborah; Reichart, Anke

    2000-01-01

    A direct assay is described using novel three-dimensional polymeric assemblies which change from a blue to red color when exposed to an analyte, in one case a flu virus. The assemblies are typically in the form of liposomes which can be maintained in a suspension, and show great intensity in their color changes. Their method of production is also described.

  1. Apple latent spherical virus vectors for reliable and effective virus-induced gene silencing among a broad range of plants including tobacco, tomato, Arabidopsis thaliana, cucurbits, and legumes

    SciTech Connect

    Igarashi, Aki; Yamagata, Kousuke; Sugai, Tomokazu; Takahashi, Yukari; Sugawara, Emiko; Tamura, Akihiro; Yaegashi, Hajime; Yamagishi, Noriko; Takahashi, Tsubasa; Isogai, Masamichi; Takahashi, Hideki; Yoshikawa, Nobuyuki

    2009-04-10

    Apple latent spherical virus (ALSV) vectors were evaluated for virus-induced gene silencing (VIGS) of endogenous genes among a broad range of plant species. ALSV vectors carrying partial sequences of a subunit of magnesium chelatase (SU) and phytoene desaturase (PDS) genes induced highly uniform knockout phenotypes typical of SU and PDS inhibition on model plants such as tobacco and Arabidopsis thaliana, and economically important crops such as tomato, legume, and cucurbit species. The silencing phenotypes persisted throughout plant growth in these plants. In addition, ALSV vectors could be successfully used to silence a meristem gene, proliferating cell nuclear antigen and disease resistant N gene in tobacco and RCY1 gene in A. thaliana. As ALSV infects most host plants symptomlessly and effectively induces stable VIGS for long periods, the ALSV vector is a valuable tool to determine the functions of interested genes among a broad range of plant species.

  2. A C. elegans-based foam for rapid on-site detection of residual live virus.

    SciTech Connect

    Negrete, Oscar A.; Branda, Catherine; Hardesty, Jasper O. E.; Tucker, Mark David; Kaiser, Julia N.; Kozina, Carol L.; Chirica, Gabriela S.

    2012-02-01

    In the response to and recovery from a critical homeland security event involving deliberate or accidental release of biological agents, initial decontamination efforts are necessarily followed by tests for the presence of residual live virus or bacteria. Such 'clearance sampling' should be rapid and accurate, to inform decision makers as they take appropriate action to ensure the safety of the public and of operational personnel. However, the current protocol for clearance sampling is extremely time-intensive and costly, and requires significant amounts of laboratory space and capacity. Detection of residual live virus is particularly problematic and time-consuming, as it requires evaluation of replication potential within a eukaryotic host such as chicken embryos. The intention of this project was to develop a new method for clearance sampling, by leveraging Sandia's expertise in the biological and material sciences in order to create a C. elegans-based foam that could be applied directly to the entire contaminated area for quick and accurate detection of any and all residual live virus by means of a fluorescent signal. Such a novel technology for rapid, on-site detection of live virus would greatly interest the DHS, DoD, and EPA, and hold broad commercial potential, especially with regard to the transportation industry.

  3. Lung Irradiation Increases Mortality After Influenza A Virus Challenge Occurring Late After Exposure

    SciTech Connect

    Manning, Casey M.; Johnston, Carl J.; Reed, Christina K.; Lawrence, B. Paige; Williams, Jacqueline P.; Finkelstein, Jacob N.

    2013-05-01

    Purpose: To address whether irradiation-induced changes in the lung environment alter responses to a viral challenge delivered late after exposure but before the appearance of late lung radiation injury. Methods and Materials: C57BL/6J mice received either lung alone or combined lung and whole-body irradiation (0-15 Gy). At 10 weeks after irradiation, animals were infected with 120 HAU influenza virus strain A/HKx31. Innate and adaptive immune cell recruitment was determined using flow cytometry. Cytokine and chemokine production and protein leakage into the lung after infection were assessed. Results: Prior irradiation led to a dose-dependent failure to regain body weight after infection and exacerbated mortality, but it did not affect virus-specific immune responses or virus clearance. Surviving irradiated animals displayed a persistent increase in total protein in bronchoalveolar lavage fluid and edema. Conclusions: Lung irradiation increased susceptibility to death after infection with influenza virus and impaired the ability to complete recovery. This altered response does not seem to be due to a radiation effect on the immune response, but it may possibly be an effect on epithelial repair.

  4. Structure of the Newcastle disease virus F protein in the post-fusion conformation

    SciTech Connect

    Swanson, Kurt; Wen, Xiaolin; Leser, George P.; Paterson, Reay G.; Lamb, Robert A.; Jardetzky, Theodore S. (Stanford-MED); (NWU); (HHMI)

    2010-11-17

    The paramyxovirus F protein is a class I viral membrane fusion protein which undergoes a significant refolding transition during virus entry. Previous studies of the Newcastle disease virus, human parainfluenza virus 3 and parainfluenza virus 5 F proteins revealed differences in the pre- and post-fusion structures. The NDV Queensland (Q) F structure lacked structural elements observed in the other two structures, which are key to the refolding and fusogenic activity of F. Here we present the NDV Australia-Victoria (AV) F protein post-fusion structure and provide EM evidence for its folding to a pre-fusion form. The NDV AV F structure contains heptad repeat elements missing in the previous NDV Q F structure, forming a post-fusion six-helix bundle (6HB) similar to the post-fusion hPIV3 F structure. Electrostatic and temperature factor analysis of the F structures points to regions of these proteins that may be functionally important in their membrane fusion activity.

  5. Identification of full-length transmitted/founder viruses and their progeny in primary HIV-1 infection

    SciTech Connect

    Korber, Bette; Hraber, Peter; Giorgi, Elena; Bhattacharya, T

    2009-01-01

    Identification of transmitted/founder virus genomes and their progeny by is a novel strategy for probing the molecular basis of HIV-1 transmission and for evaluating the genetic imprint of viral and host factors that act to constrain or facilitate virus replication. Here, we show in a cohort of twelve acutely infected subjects (9 clade B; 3 clade C), that complete genomic sequences of transmitted/founder viruses could be inferred using single genome amplification of plasma viral RNA, direct amplicon sequencing, and a model of random virus evolution. This allowed for the precise identification, chemical synthesis, molecular cloning, and biological analysis of those viruses actually responsible for productive clinical infection and for a comprehensive mapping of sequential viral genomes and proteomes for mutations that are necessary or incidental to the establishment of HIV-1 persistence. Transmitted/founder viruses were CD4 and CCR5 tropic, replicated preferentially in activated primary T-Iymphocytes but not monocyte-derived macrophages, and were effectively shielded from most heterologous or broadly neutralizing antibodies. By 3 months of infection, the evolving viral quasispecies in three subjects showed mutational fixation at only 2-5 discreet genomic loci. By 6-12 months, mutational fixation was evident at 18-27 genomic loci. Some, but not all, of these mutations were attributable to virus escape from cytotoxic Tlymphocytes or neutralizing antibodies, suggesting that other viral or host factors may influence early HIV -1 fitness.

  6. Surveillance for Western equine encephalitis St. Louis encephalitis and West Nile viruses using reverse transcription loop-mediated isothermal amplification

    DOE PAGES [OSTI]

    Meagher, Robert J.; Ball, Cameron Scott; Langevin, Stanley A.; Fang, Ying; Wheeler, Sarah S.; Coffey, Lark L.

    2016-01-25

    In this study, collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized publicmore » health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3’ untranslated region (3’-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance.« less

  7. Inhibition of herpes simplex virus type 1 entry by chloride channel inhibitors tamoxifen and NPPB

    SciTech Connect

    Zheng, Kai; Chen, Maoyun; Xiang, Yangfei; Ma, Kaiqi; Jin, Fujun; Wang, Xiao; Wang, Xiaoyan; Wang, Shaoxiang; Wang, Yifei

    2014-04-18

    Highlights: • We analyze the anti-HSV potential of chloride channel inhibitors. • Tamoxifen and NPPB show anti-HSV-1 and anti-ACV-resistant HSV-1 activities. • HSV-1 infection induces intracellular chloride concentration increasing. • Tamoxifen and NPPB inhibit HSV-1 early infection. • Tamoxifen and NPPB prevent the fusion process of HSV-1. - Abstract: Herpes simplex virus type 1 (HSV-1) infection is very common worldwide and can cause significant health problems from periodic skin and corneal lesions to encephalitis. Appearance of drug-resistant viruses in clinical therapy has made exploring novel antiviral agents emergent. Here we show that chloride channel inhibitors, including tamoxifen and 5-nitro-2-(3-phenyl-propylamino) benzoic acid (NPPB), exhibited extensive antiviral activities toward HSV-1 and ACV-resistant HSV viruses. HSV-1 infection induced chloride ion influx while treatment with inhibitors reduced the increase of intracellular chloride ion concentration. Pretreatment or treatment of inhibitors at different time points during HSV-1 infection all suppressed viral RNA synthesis, protein expression and virus production. More detailed studies demonstrated that tamoxifen and NPPB acted as potent inhibitors of HSV-1 early entry step by preventing viral binding, penetration and nuclear translocation. Specifically the compounds appeared to affect viral fusion process by inhibiting virus binding to lipid rafts and interrupting calcium homeostasis. Taken together, the observation that tamoxifen and NPPB can block viral entry suggests a stronger potential for these compounds as well as other ion channel inhibitors in antiviral therapy against HSV-1, especially the compound tamoxifen is an immediately actionable drug that can be reused for treatment of HSV-1 infections.

  8. Ocean Viruses: Tiny entities with Global Impacts ( JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    ScienceCinema

    Sullivan, Matthew B [University of Arizona

    2016-07-12

    Matt Sullivan from the University of Arizona on "Ocean Viruses: Tiny Entities with Global Impacts" at the 7th Annual Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, Calif.

  9. Ocean Viruses: Tiny entities with Global Impacts ( JGI Seventh Annual User Meeting 2012: Genomics of Energy and Environment)

    SciTech Connect

    Sullivan, Matthew B [University of Arizona] [University of Arizona

    2012-03-22

    Matt Sullivan from the University of Arizona on "Ocean Viruses: Tiny Entities with Global Impacts" at the 7th Annual Genomics of Energy & Environment Meeting on March 22, 2012 in Walnut Creek, Calif.

  10. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

    DOE PAGES [OSTI]

    Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.; Amos, Joshua  D.; Kumar, Amit; Hora, Bhavna; Marshall, Dawn  J.; Whitesides, John  F.; Xia, Shi-Mao; Parks, Robert; et al

    2015-09-09

    The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tiermore » 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.« less

  11. Strain-Specific V3 and CD4 Binding Site Autologous HIV-1 Neutralizing Antibodies Select Neutralization-Resistant Viruses

    SciTech Connect

    Moody, M.  Anthony; Gao, Feng; Gurley, Thaddeus  C.; Amos, Joshua  D.; Kumar, Amit; Hora, Bhavna; Marshall, Dawn  J.; Whitesides, John  F.; Xia, Shi-Mao; Parks, Robert; Lloyd, Krissey  E.; Hwang, Kwan-Ki; Lu, Xiaozhi; Bonsignori, Mattia; Finzi, Andrés; Vandergrift, Nathan  A.; Alam, S.  Munir; Ferrari, Guido; Shen, Xiaoying; Tomaras, Georgia  D.; Kamanga, Gift; Cohen, Myron  S.; Sam, Noel  E.; Kapiga, Saidi; Gray, Elin S.; Tumba, Nancy  L.; Morris, Lynn; Zolla-Pazner, Susan; Gorny, Miroslaw  K.; Mascola, John  R.; Hahn, Beatrice H.; Shaw, George  M.; Sodroski, Joseph  G.; Liao, Hua-Xin; Montefiori, David C.; Hraber, Peter T.; Korber, Bette T.; Haynes, Barton F.

    2015-09-09

    The third variable (V3) loop and the CD4 binding site (CD4bs) of the viral envelope are frequently targeted by neutralizing antibodies (nAbs) in HIV-1-infected individuals. In chronic infection, virus escape mutants repopulate the plasma and V3 and CD4bs nAbs emerge that can neutralize heterologous tier 1 easy-to-neutralize, but not tier 2 difficult-to-neutralize HIV-1 isolates. However, neutralization sensitivity of autologous plasma viruses to this type of nAb response has not been studied. We describe the development and evolution in vivo of antibodies distinguished by their target specificity for V3and CD4bs epitopes on autologous tier 2 viruses but not on heterologous tier 2 viruses. A surprisingly high fraction of autologous circulating viruses was sensitive to these antibodies. These findings demonstrate a role for V3 and CD4bs antibodies in constraining the native envelope trimer in vivo to a neutralization-resistant phenotype, explaining why HIV-1 transmission generally occurs by tier 2 neutralization-resistant viruses.

  12. Lettuce infectious yellows virus-encoded P26 induces plasmalemma deposit cytopathology

    SciTech Connect

    Stewart, Lucy R.; Medina, Vicente; Sudarshana, Mysore R.; Falk, Bryce W.

    2009-05-25

    Lettuce infectious yellows virus (LIYV) encodes a 26 kDa protein (P26) previously shown to associate with plasmalemma deposits (PLDs), unique LIYV-induced cytopathologies located at the plasmalemma over plasmodesmata pit fields in companion cells and phloem parenchyma. To further characterize the relationship of P26 and PLDs, we assessed localization and cytopathology induction of P26 expressed from either LIYV or a heterologous Tobacco mosaic virus (TMV) vector using green fluorescent protein (GFP) fusions, immunofluorescence microscopy, biochemical fractionation, and transmission electron microscopy (TEM). TEM analyses demonstrated that P26 not only associated with, but induced formation of PLDs in the absence of other LIYV proteins. Interestingly, PLDs induced by P26-expressing TMV were no longer confined to phloem cells. Putative P26 orthologs from two other members of the genus Crinivirus which do not induce conspicuous PLDs exhibited fractionation properties similar to LIYV P26 but were not associated with any PLD-like cytopathology.

  13. Perspectives on West Africa Ebola Virus Disease Outbreak, 2013-2016

    DOE PAGES [OSTI]

    Spengler, Jessica R.; Ervin, Elizabeth D.; Towner, Jonathan S.; Rollin, Pierre E.; Nichol, Stuart T.

    2016-06-01

    The variety of factors that contributed to the initial undetected spread of Ebola virus disease in West Africa during 2013-2016 and the difficulty controlling the outbreak once the etiology was identified highlight priorities for disease prevention, detection, and response. These factors include occurrence in a region recovering from civil instability and lacking experience with Ebola response; inadequate surveillance, recognition of suspected cases, and Ebola diagnosis; mobile populations and extensive urban transmission; and the community's insufficient general understanding about the disease. The magnitude of the outbreak was not attributable to a substantial change of the virus. Finally, continued efforts during themore » outbreak and in preparation for future outbreak response should involve identifying the reservoir, improving in-country detection and response capacity, conducting survivor studies and supporting survivors, engaging in culturally appropriate public education and risk communication, building productive interagency relationships, and continuing support for basic research.« less

  14. Metabolism and expression of RNA polymerase II transcripts in Influenza virus-infected cells

    SciTech Connect

    Katze, M.G.; Krug, R.M.

    1984-10-01

    Influenza virus infection has adverse effects on the metabolism of two representative RNA polymerase II transcripts in chicken embryo fibroblasts, those coding for BETA-actin and for avian leukosis virus (ALV) proteins. Proviral ALV DNA was integrated into host cell DNA by prior infection with ALV. By S1 endonuclease assay, it was confirmed that nuclear ALV transcripts disappeared very early after infection, already decreasing ca. 80% by 1 h postinfection. A plausible explanation for this nuclear degradation is that the viral cap-dependent endonuclease in the nucleas cleaves the 5' ends of new polymerase II transcripts, rendering the resulting decapped RNAs susceptible to hydrolysis by cellular nucleases. Similar stability of cytoplasmic host cell mRNAs was observed in infected HeLa cells, in which the levels of actin mRNA and two HeLa cell mRNAs (pHe 7 and pHe 28) remained at undiminished levels for 3 h of infection and decreased only slightly by 4.5 h postinfection. The cytoplamic actin and pHe 7 mRNAs isolated from infected HeLa cells were shown to be translated in reticulocyte extracts in biro, indicating that host mRNAs were not inactivated by a virus-induced modification. Despite the continued presence of high levels of functional host cell mRNAs, host cell protein synthesis was effectively shut off by about 3 h postinfection in both chicken embryo fibroblasts and HeLa cells. These results are consistent with the establishment of an influenza virus-specific translational system that selectively translates viral and not host mRNAs.

  15. Effect of 1918 PB1-F2 expression on influenza A virus infection kinetics

    SciTech Connect

    Ribeiro, Ruy; Perelson, Alan S; Smith, Amber M; Adler, Frederick R; Mcauley, Julie L; Mccullers, Jonathan A

    2009-01-01

    Relatively little is known about the viral factors contributing to the lethality of the 1918 pandemic, although its unparalleled virulence was likely due in part to the newly discovered PB1-F2 protein. This protein, while unnecessary for replication, increases apoptosis in monocytes, alters viral polymerase activity in vitro, and produces enhanced inflammation and increased secondary pneumonia in vivo. However, the effects the PB1-F2 protein have in vivo remain unclear. To address the mechanisms involved, we intranasally infected groups of mice with either influenza A virus PR8 or a genetically engineered virus that expresses the 1918 PB1-F2 protein on a PR8 background, PR8-PB1-F2(1918). Mice inoculated with PR8 had viral concentrations peaking at 72 hours, while those infected with PR8-PB1-F2(1918) reached peak concentrations earlier, 48 hours. Mice given PR8-PB1-F2(1918) also showed a faster decline in viral loads. We fit a mathematical model to these data to estimate parameter values and select the best model. This model supports a lower viral clearance rate and higher infected cell death rate with the PR8-PB1-F2(1918) virus, although the viral production rate may also be higher. We hypothesize that the higher PR8-PB1-F2(1918) viral titers early in an infection are due to both an increase in viral production with decreased viral clearance, and that the faster decline in the later stages of infection result from elevated cell death rates. We discuss the implications these mechanisms have during an infection with a virus expressing a virulent PBI-F2 on the possibility of a pandemic and on the importance of antiviral treatments.

  16. Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients

    SciTech Connect

    Yue, Ling; Pfafferott, Katja J.; Baalwa, Joshua; Conrod, Karen; Dong, Catherine C.; Chui, Cecilia; Rong, Rong; Claiborne, Daniel T.; Prince, Jessica L.; Tang, Jianming; Ribeiro, Ruy M.; Cormier, Emmanuel; Hahn, Beatrice H.; Perelson, Alan S.; Shaw, George M.; Karita, Etienne; Gilmour, Jill; Goepfert, Paul; Derdeyn, Cynthia A.; Allen, Susan A.; Borrow, Persephone; Hunter, Eric; Douek, Daniel C.

    2015-01-08

    Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/founder (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a

  17. Transmitted virus fitness and host T cell responses collectively define divergent infection outcomes in two HIV-1 recipients

    DOE PAGES [OSTI]

    Yue, Ling; Pfafferott, Katja J.; Baalwa, Joshua; Conrod, Karen; Dong, Catherine C.; Chui, Cecilia; Rong, Rong; Claiborne, Daniel T.; Prince, Jessica L.; Tang, Jianming; et al

    2015-01-08

    Control of virus replication in HIV-1 infection is critical to delaying disease progression. While cellular immune responses are a key determinant of control, relatively little is known about the contribution of the infecting virus to this process. To gain insight into this interplay between virus and host in viral control, we conducted a detailed analysis of two heterosexual HIV-1 subtype A transmission pairs in which female recipients sharing three HLA class I alleles exhibited contrasting clinical outcomes: R880F controlled virus replication while R463F experienced high viral loads and rapid disease progression. Near full-length single genome amplification defined the infecting transmitted/foundermore » (T/F) virus proteome and subsequent sequence evolution over the first year of infection for both acutely infected recipients. T/F virus replicative capacities were compared in vitro, while the development of the earliest cellular immune response was defined using autologous virus sequence-based peptides. The R880F T/F virus replicated significantly slower in vitro than that transmitted to R463F. While neutralizing antibody responses were similar in both subjects, during acute infection R880F mounted a broad T cell response, the most dominant components of which targeted epitopes from which escape was limited. In contrast, the primary HIV-specific T cell response in R463F was focused on just two epitopes, one of which rapidly escaped. This comprehensive study highlights both the importance of the contribution of the lower replication capacity of the transmitted/founder virus and an associated induction of a broad primary HIV-specific T cell response, which was not undermined by rapid epitope escape, to long-term viral control in HIV-1 infection. It underscores the importance of the earliest CD8 T cell response targeting regions of the virus proteome that cannot mutate without a high fitness cost, further emphasizing the need for vaccines that elicit a breadth of

  18. Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population

    SciTech Connect

    Immonen, Taina T.; Conway, Jessica M.; Romero-Severson, Ethan O.; Perelson, Alan S.; Leitner, Thomas; Kouyos, Roger Dimitri

    2015-12-22

    HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune response an advantage. Virus released from activated latent cells competes against variants that have continually evolved and adapted to host immune pressure. Nevertheless, there is increasing evidence that virus displaying a signal of latency survives in patient plasma despite having reduced fitness due to long-term immune memory. We investigated the survival of virus with latent envelope genomic fragments by simulating within-host HIV-1 sequence evolution and the cycling of viral lineages in and out of the latent reservoir. Our model incorporates a detailed mutation process including nucleotide substitution, recombination, latent reservoir dynamics, diversifying selection pressure driven by the immune response, and purifying selection pressure asserted by deleterious mutations. We evaluated the ability of our model to capture sequence evolution in vivo by comparing our simulated sequences to HIV-1 envelope sequence data from 16 HIV-infected untreated patients. Empirical sequence divergence and diversity measures were qualitatively and quantitatively similar to those of our simulated HIV-1 populations, suggesting that our model invokes realistic trends of HIV-1 genetic evolution. Moreover, reconstructed phylogenies of simulated and patient HIV-1 populations showed similar topological structures. Our simulation results suggest that recombination is a key mechanism facilitating the persistence of virus with latent envelope genomic fragments in the productively infected cell population. Recombination increased the survival probability of latent virus forms approximately 13-fold. Prevalence of virus with latent fragments in productively infected cells was observed in only 2% of simulations when we ignored recombination, while the proportion increased to 27% of simulations when we allowed recombination. We also found that the selection pressures exerted by different fitness

  19. Mutations Abrogating VP35 Interaction with Double-Stranded RNA Render Ebola Virus Avirulent in Guinea Pigs

    SciTech Connect

    Prins, Kathleen C.; Delpeut, Sebastien; Leung, Daisy W.; Reynard, Olivier; Volchkova, Valentina A.; Reid, St. Patrick; Ramanan, Parameshwaran; Cárdenas, Washington B.; Amarasinghe, Gaya K.; Volchkov, Viktor E.; Basler, Christopher F.

    2010-10-11

    Ebola virus (EBOV) protein VP35 is a double-stranded RNA (dsRNA) binding inhibitor of host interferon (IFN)-{alpha}/{beta} responses that also functions as a viral polymerase cofactor. Recent structural studies identified key features, including a central basic patch, required for VP35 dsRNA binding activity. To address the functional significance of these VP35 structural features for EBOV replication and pathogenesis, two point mutations, K319A/R322A, that abrogate VP35 dsRNA binding activity and severely impair its suppression of IFN-{alpha}/{beta} production were identified. Solution nuclear magnetic resonance (NMR) spectroscopy and X-ray crystallography reveal minimal structural perturbations in the K319A/R322A VP35 double mutant and suggest that loss of basic charge leads to altered function. Recombinant EBOVs encoding the mutant VP35 exhibit, relative to wild-type VP35 viruses, minimal growth attenuation in IFN-defective Vero cells but severe impairment in IFN-competent cells. In guinea pigs, the VP35 mutant virus revealed a complete loss of virulence. Strikingly, the VP35 mutant virus effectively immunized animals against subsequent wild-type EBOV challenge. These in vivo studies, using recombinant EBOV viruses, combined with the accompanying biochemical and structural analyses directly correlate VP35 dsRNA binding and IFN inhibition functions with viral pathogenesis. Moreover, these studies provide a framework for the development of antivirals targeting this critical EBOV virulence factor.

  20. Evolution of plant virus movement proteins from the 30K superfamily and of their homologs integrated in plant genomes

    SciTech Connect

    Mushegian, Arcady R.; Elena, Santiago F.

    2015-02-15

    Homologs of Tobacco mosaic virus 30K cell-to-cell movement protein are encoded by diverse plant viruses. Mechanisms of action and evolutionary origins of these proteins remain obscure. We expand the picture of conservation and evolution of the 30K proteins, producing sequence alignment of the 30K superfamily with the broadest phylogenetic coverage thus far and illuminating structural features of the core all-beta fold of these proteins. Integrated copies of pararetrovirus 30K movement genes are prevalent in euphyllophytes, with at least one copy intact in nearly every examined species, and mRNAs detected for most of them. Sequence analysis suggests repeated integrations, pseudogenizations, and positive selection in those provirus genes. An unannotated 30K-superfamily gene in Arabidopsis thaliana genome is likely expressed as a fusion with the At1g37113 transcript. This molecular background of endopararetrovirus gene products in plants may change our view of virus infection and pathogenesis, and perhaps of cellular homeostasis in the hosts. - Highlights: • Sequence region shared by plant virus “30K” movement proteins has an all-beta fold. • Most euphyllophyte genomes contain integrated copies of pararetroviruses. • These integrated virus genomes often include intact movement protein genes. • Molecular evidence suggests that these “30K” genes may be selected for function.

  1. Structure of the paramyxovirus parainfluenza virus 5 nucleoprotein-?RNA complex

    SciTech Connect

    Alayyoubi, Maher; Leser, George P.; Kors, Christopher A.; Lamb, Robert A.

    2015-04-07

    Parainfluenza virus 5 (PIV5) is a member of the Paramyxoviridae family of membrane-enveloped viruses with a negative-sense RNA genome that is packaged and protected by long filamentous nucleocapsid-helix structures (RNPs). These RNPs, consisting of ~2,600 protomers of nucleocapsid (N) protein, form the template for viral transcription and replication. We have determined the 3D X-ray crystal structure of the nucleoprotein (N)-RNA complex from PIV5 to 3.11- resolution. The structure reveals a 13-mer nucleocapsid ring whose diameter, cavity, and pitch/height dimensions agree with EM data from early studies on the Paramyxovirinae subfamily of native RNPs, indicating that it closely represents one-turn in the building block of the RNP helices. The PIV5-N nucleocapsid ring encapsidates a nuclease resistant 78-nt RNA strand in its positively charged groove formed between the N-terminal (NTD) and C-terminal (CTD) domains of its successive N protomers. Six nucleotides precisely are associated with each N protomer, with alternating three-base-in three-base-out conformation. The binding of six nucleotides per protomer is consistent with the "rule of six" that governs the genome packaging of the Paramyxovirinae subfamily of viruses. PIV5-N protomer subdomains are very similar in structure to the previously solved Nipah-N structure, but with a difference in the angle between NTD/CTD at the RNA hinge region. Based on the Nipah-N structure we modeled a PIV5-N open conformation in which the CTD rotates away from the RNA strand into the inner spacious nucleocapsid-ring cavity. This rotation would expose the RNA for the viral polymerase activity without major disruption of the nucleocapsid structure.

  2. Surface localization of the nuclear receptor CAR in influenza A virus-infected cells

    SciTech Connect

    Takahashi, Tadanobu; Moriyama, Yusuke; Ikari, Akira; Sugatani, Junko; Suzuki, Takashi; Miwa, Masao

    2008-04-11

    Constitutive active/androstane receptor CAR is a member of the nuclear receptors which regulate transcription of xenobiotic metabolism enzymes. CAR is usually localized in the cytosol and nucleus. Here, we found that CAR was localized at the cell surface of influenza A virus (IAV)-infected cells. Additionally, we demonstrated that expression of a viral envelope glycoprotein, either hemagglutinin (HA) or neuraminidase (NA), but not viral nucleoprotein (NP), was responsible for this localization. This report is the first demonstration of CAR at the surface of tissue culture cells, and suggests that CAR may exert the IAV infection mechanism.

  3. Effects of UVA irradiation, aryl azides, and reactive oxygen species on the orthogonal inactivation of the human immunodeficiency virus (HIV-1)

    SciTech Connect

    Belanger, Julie M.; Raviv, Yossef; Viard, Mathias; Cruz, M. Jason de la; Nagashima, Kunio; Blumenthal, Robert

    2011-08-15

    Previously we reported that hydrophobic aryl azides partition into hydrophobic regions of the viral membrane of enveloped viruses and inactivate the virus upon UVA irradiation for 2 min. Prolonged irradiation (15 min) resulted in viral protein aggregation as visualized via Western blot analysis, due to reactive oxygen species (ROS) formation, with preservation of the surface antigenic epitopes. Herein, we demonstrate that these aggregates show detergent resistance and that this property may be useful towards the creation of a novel orthogonal virus inactivation strategy for use in preparing experimental vaccines. When ROS-modified HIV virus preparations were treated with 1% Triton X-100, there was an increase in the percent of viral proteins (gp41, p24) in the viral pellet after ultracentrifugation through sucrose. Transmission electron microscopy (TEM) of these detergent-resistant pellets shows some recognizable virus fragments, and immunoprecipitation studies of the gp41 aggregates suggest the aggregation is covalent in nature, involving short-range interactions.

  4. The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

    SciTech Connect

    Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaeelle; Frobert, Emilie; Yver, Matthieu; Traversier, Aurelien; Wolff, Thorsten; Naffakh, Nadia; and others

    2012-10-10

    Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus-host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

  5. Genomics-enabled sensor platform for rapid detection of viruses related to disease outbreak.

    SciTech Connect

    Brozik, Susan Marie; Manginell, Ronald Paul; Moorman, Matthew Wallace; Xiao, Xiaoyin; Edwards, Thayne L.; Anderson, John Moses; Pfeifer, Kent Bryant; Branch, Darren W.; Wheeler, David Roger; Polsky, Ronen; Lopez, DeAnna M.; Ebel, Gregory D.; Prasad, Abhishek N.; Brozik, James A.; Rudolph, Angela R.; Wong, Lillian P.

    2013-09-01

    Bioweapons and emerging infectious diseases pose growing threats to our national security. Both natural disease outbreak and outbreaks due to a bioterrorist attack are a challenge to detect, taking days after the outbreak to identify since most outbreaks are only recognized through reportable diseases by health departments and reports of unusual diseases by clinicians. In recent decades, arthropod-borne viruses (arboviruses) have emerged as some of the most significant threats to human health. They emerge, often unexpectedly, from cryptic transmission foci causing localized outbreaks that can rapidly spread to multiple continents due to increased human travel and trade. Currently, diagnosis of acute infections requires amplification of viral nucleic acids, which can be costly, highly specific, technically challenging and time consuming. No diagnostic devices suitable for use at the bedside or in an outbreak setting currently exist. The original goals of this project were to 1) develop two highly sensitive and specific diagnostic assays for detecting RNA from a wide range of arboviruses; one based on an electrochemical approach and the other a fluorescent based assay and 2) develop prototype microfluidic diagnostic platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were developed for DNA-RNA hybridization detection and were implemented in microfluidic diagnostic sensing platforms that were developed in this project.

  6. Dynamics of lipid droplets induced by the hepatitis C virus core protein

    SciTech Connect

    Lyn, Rodney K.; Department of Chemistry, University of Ottawa, Ottawa ; Kennedy, David C.; Stolow, Albert; Ridsdale, Andrew; Pezacki, John Paul

    2010-09-03

    Research highlights: {yields} Hepatitis C virus uses lipid droplets (LD) onto which HCV core proteins bind. {yields} HCV core proteins on LDs facilitate viral particle assembly. {yields} We used a novel combination of CARS, two-photon fluorescence, and DIC microscopies. {yields} Particle tracking experiments show that core slowly affects LD localization. {yields} Particle tracking measured the change in speed and directionality of LD movement. -- Abstract: The hepatitis C virus (HCV) is a global health problem, with limited treatment options and no vaccine available. HCV uses components of the host cell to proliferate, including lipid droplets (LD) onto which HCV core proteins bind and facilitate viral particle assembly. We have measured the dynamics of HCV core protein-mediated changes in LDs and rates of LD movement on microtubules using a combination of coherent anti-Stokes Raman scattering (CARS), two-photon fluorescence (TPF), and differential interference contrast (DIC) microscopies. Results show that the HCV core protein induces rapid increases in LD size. Particle tracking experiments show that HCV core protein slowly affects LD localization by controlling the directionality of LD movement on microtubules. These dynamic processes ultimately aid HCV in propagating and the molecules and interactions involved represent novel targets for potential therapeutic intervention.

  7. The minute virus of mice exploits different endocytic pathways for cellular uptake

    SciTech Connect

    Garcin, Pierre O.; Panté, Nelly

    2015-08-15

    The minute virus of mice, prototype strain (MVMp), is a non-enveloped, single-stranded DNA virus of the family Parvoviridae. Unlike other parvoviruses, the mechanism of cellular uptake of MVMp has not been studied in detail. We analyzed MVMp endocytosis in mouse LA9 fibroblasts and a tumor cell line derived from epithelial–mesenchymal transition through polyomavirus middle T antigen transformation in transgenic mice. By a combination of immunofluorescence and electron microscopy, we found that MVMp endocytosis occurs at the leading edge of migrating cells in proximity to focal adhesion sites. By using drug inhibitors of various endocytic pathways together with immunofluorescence microscopy and flow cytometry analysis, we discovered that MVMp can use a number of endocytic pathways, depending on the host cell type. At least three different mechanisms were identified: clathrin-, caveolin-, and clathrin-independent carrier-mediated endocytosis, with the latter occurring in transformed cells but not in LA9 fibroblasts. - Highlights: • MVMp uptake takes place at the leading edge of migrating cells. • MVMp exploits a variety of endocytic pathways. • MVMp could use clathrin- and caveolin-mediated endocytosis. • MVMp could also use clathrin-independent carriers for cellular uptake.

  8. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    SciTech Connect

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  9. Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus population

    DOE PAGES [OSTI]

    Immonen, Taina T.; Conway, Jessica M.; Romero-Severson, Ethan O.; Perelson, Alan S.; Leitner, Thomas; Kouyos, Roger Dimitri

    2015-12-22

    HIV-1 is subject to immune pressure exerted by the host, giving variants that escape the immune response an advantage. Virus released from activated latent cells competes against variants that have continually evolved and adapted to host immune pressure. Nevertheless, there is increasing evidence that virus displaying a signal of latency survives in patient plasma despite having reduced fitness due to long-term immune memory. We investigated the survival of virus with latent envelope genomic fragments by simulating within-host HIV-1 sequence evolution and the cycling of viral lineages in and out of the latent reservoir. Our model incorporates a detailed mutation processmore » including nucleotide substitution, recombination, latent reservoir dynamics, diversifying selection pressure driven by the immune response, and purifying selection pressure asserted by deleterious mutations. We evaluated the ability of our model to capture sequence evolution in vivo by comparing our simulated sequences to HIV-1 envelope sequence data from 16 HIV-infected untreated patients. Empirical sequence divergence and diversity measures were qualitatively and quantitatively similar to those of our simulated HIV-1 populations, suggesting that our model invokes realistic trends of HIV-1 genetic evolution. Moreover, reconstructed phylogenies of simulated and patient HIV-1 populations showed similar topological structures. Our simulation results suggest that recombination is a key mechanism facilitating the persistence of virus with latent envelope genomic fragments in the productively infected cell population. Recombination increased the survival probability of latent virus forms approximately 13-fold. Prevalence of virus with latent fragments in productively infected cells was observed in only 2% of simulations when we ignored recombination, while the proportion increased to 27% of simulations when we allowed recombination. We also found that the selection pressures exerted by different

  10. Synergized resmethrin and corticosterone alter the chicken's response to west nile virus

    SciTech Connect

    Jankowski, Mark David; Franson, J Christian; Mostl, Erich; Porter, Warren P; Hofmeister, Erik K

    2009-01-01

    Debate concerning arbovirus control strategies remains contentious because concern regarding the relative risk of viral infection and environmental toxicant exposure is high but inadequately characterized. Taking this into account, mosquito control agencies employ aerial insecticides only after arbovirus surveillance data indicate high local mosquito-infection-rates. Successfully mitigating the risk of adult-mosquito-control insecticides ('adulticides') to non-target species such as humans, domestic animals, fish, beneficial insects and wildlife, while increasing their efficacy to reduce arbovirus outbreak intensity requires targeted scientific data from animal toxicity studies and environmental monitoring activities. Wild birds are an important reservoir host for WNv and are potentially exposed to insecticides used for mosquito control. However, no risk assessments have evaluated whether insecticides augment or extend the potential transmissibility of West Nile virus (WNv) in birds. In order to augment existing resmethrin risk assessments, we aimed to determine whether synergized resmethrin (SR) may cause chickens to develop an elevated or extended WN viremia and if subacute stress may affect its immunotoxicity. We distributed 40 chickens into four groups then exposed them prior to and during WNv infection with SR (50 {mu}g/l resmethrin + 150 {mu}g/l piperonyl butoxide) and/or 20 mg/I corticosterone (CORT) in their drinking-water. Corticosterone was given for 10 continuous days and SR was given for 3 alternate days starting the 3rd day of CORT exposure, then chickens were subcutaneously inoculated with WNv on the 5th day of CORT treatment. Compared to controls, CORT treatment extended and elevated viremia, enhanced WNv-specific antibody and increased the percentage of birds that shed oral virus, whereas SR treatment extended viremia, depressed WNv-specific IgG, and increased the percentage of CORT-treated birds that shed oral virus. Corticosterone and SR

  11. Improving the Capacity of Sodium Ion Battery Using a Virus-Templated Nanostructured Composite Cathode

    SciTech Connect

    Moradi, M; Li, Z; Qi, JF; Xing, WT; Xiang, K; Chiang, YM; Belcher, AM

    2015-05-01

    In this work we investigated an energy-efficient biotemplated route to synthesize nanostructured FePO4 for sodium-based batteries. Self-assembled M13 viruses and single wall carbon nanotubes (SWCNTs) have been used as a template to grow amorphous FePO4 nanoparticles at room temperature (the active composite is denoted as Bio-FePO4-CNT) to enhance the electronic conductivity of the active material. Preliminary tests demonstrate a discharge capacity as high as 166 mAh/g at C/10 rate, corresponding to composition Na0.9FePO4, which along with higher C-rate tests show this material to have the highest capacity and power performance reported for amorphous FePO4 electrodes to date.

  12. Relative concordance of human immunodeficiency virus oligomeric and monomeric envelope in CCR5 coreceptor usage

    SciTech Connect

    Teeravechyan, Samaporn; Suphaphiphat, Pirada; Essex, Max; Lee, Tun-Hou

    2008-01-20

    A major difference between binding and fusion assays commonly used to study the human immunodeficiency virus (HIV) envelope is the use of monomeric envelope for the former assay and oligomeric envelope for the latter. Due to discrepancies in their readouts for some mutants, envelope regions involved in CCR5 coreceptor usage were systematically studied to determine whether the discordance is due to inherent differences between the two assays or whether it genuinely reflects functional differences at each entry step. By adding the binding inhibitor TAK-779 to delay coreceptor binding kinetics in the fusion assay, the readouts were found comparable between the assays for the mutants analysed in this study. Our finding indicates that monomeric binding reflects oligomeric envelope-CCR5 interaction, thus discordant results between binding and fusion assays do not necessarily indicate differences in coreceptor usage by oligomeric envelope and monomeric gp120.

  13. Tetraodon nigroviridis as a nonlethal model of infectious spleen and kidney necrosis virus (ISKNV) infection

    SciTech Connect

    Xu Xiaopeng; Huang Lichao; Weng Shaoping; Wang Jing; Lin Ting; Tang Junliang; Li Zhongsheng; Lu Qingxia; Xia Qiong; Yu Xiaoqiang; He Jianguo

    2010-10-25

    Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus, family Iridoviridae. We have previously established a high mortality ISKNV infection model of zebrafish (Danio rerio). In this study, a nonlethal Tetraodon nigroviridis model of ISKNV infection was established. ISKNV infection did not cause lethal disease in Tetraodon but could infect almost all the organs of this species. Electron microscopy showed ISKNV particles were present in infected tissues. Immunofluorescence and quantitative real-time PCR analysis showed that nearly all the virions and infected cells were cleared at 14 d postinfection. The expression profiles of interferon-{gamma} and tumor necrosis factor-{alpha} gene in response to ISKNV infection were significantly different in Tetraodon and zebrafish. The establishment of the nonlethal Tetraodon model of ISKNV infection can offer a valuable tool complementary to the zebrafish infection model for studying megalocytivirus disease, fish immune systems, and viral tropism.

  14. Myxoma and vaccinia viruses exploit different mechanisms to enter and infect human cancer cells

    SciTech Connect

    Villa, Nancy Y.; Bartee, Eric; Mohamed, Mohamed R.; Rahman, Masmudur M.; Barrett, John W.; McFadden, Grant

    2010-06-05

    Myxoma (MYXV) and vaccinia (VACV) viruses have recently emerged as potential oncolytic agents that can infect and kill different human cancer cells. Although both are structurally similar, it is unknown whether the pathway(s) used by these poxviruses to enter and cause oncolysis in cancer cells are mechanistically similar. Here, we compared the entry of MYXV and VACV-WR into various human cancer cells and observed significant differences: 1 - low-pH treatment accelerates fusion-mediated entry of VACV but not MYXV, 2 - the tyrosine kinase inhibitor genistein inhibits entry of VACV, but not MYXV, 3 - knockdown of PAK1 revealed that it is required for a late stage event downstream of MYXV entry into cancer cells, whereas PAK1 is required for VACV entry into the same target cells. These results suggest that VACV and MYXV exploit different mechanisms to enter into human cancer cells, thus providing some rationale for their divergent cancer cell tropisms.

  15. Cell cycle regulation of human immunodeficiency virus type 1 integration in T cells: antagonistic effects of nuclear envelope breakdown and chromatin condensation

    SciTech Connect

    Mannioui, Abdelkrim . E-mail: karim.mannioui@chu-stlouis.fr; Schiffer, Cecile . E-mail: cecile.schiffer@voila.fr; Felix, Nathalie . E-mail: nathalie.felix@chu-stlouis.fr

    2004-11-10

    We examined the influence of mitosis on the kinetics of human immunodeficiency virus type 1 integration in T cells. Single-round infection of cells arrested in G1b or allowed to synchronously proceed through division showed that mitosis delays virus integration until 18-24 h postinfection, whereas integration reaches maximum levels by 15 h in G1b-arrested cells. Subcellular fractionation of metaphase-arrested cells indicated that, while nuclear envelope disassembly facilitates docking of viral DNA to chromatin, chromosome condensation directly antagonizes and therefore delays integration. As a result of the balance between the two effects, virus integration efficiency is eventually up to threefold greater in dividing cells. At the single-cell level, using a green fluorescent protein-expressing reporter virus, we found that passage through mitosis leads to prominent asymmetric segregation of the viral genome in daughter cells without interfering with provirus expression.

  16. Analytical Performance Characteristics of the Cepheid GeneXpert Ebola Assay for the Detection of Ebola Virus

    DOE PAGES [OSTI]

    Pinsky, Benjamin A.; Sahoo, Malaya K.; Sandlund, Johanna; Kleman, Marika; Kulkarni, Medha; Grufman, Per; Nygren, Malin; Kwiatkowski, Robert; Baron, Ellen Jo; Tenover, Fred; et al

    2015-11-12

    The recently developed Xpert® Ebola Assay is a novel nucleic acid amplification test for simplified detection of Ebola virus (EBOV) in whole blood and buccal swab samples. The assay targets sequences in two EBOV genes, lowering the risk for new variants to escape detection in the test. The objective of this report is to present analytical characteristics of the Xpert® Ebola Assay on whole blood samples. Our study evaluated the assay’s analytical sensitivity, analytical specificity, inclusivity and exclusivity performance in whole blood specimens. EBOV RNA, inactivated EBOV, and infectious EBOV were used as targets. The dynamic range of the assay,more » the inactivation of virus, and specimen stability were also evaluated. The lower limit of detection (LoD) for the assay using inactivated virus was estimated to be 73 copies/mL (95% CI: 51–97 copies/mL). The LoD for infectious virus was estimated to be 1 plaque-forming unit/mL, and for RNA to be 232 copies/mL (95% CI 163–302 copies/mL). The assay correctly identified five different Ebola viruses, Yambuku-Mayinga, Makona-C07, Yambuku-Ecran, Gabon-Ilembe, and Kikwit-956210, and correctly excluded all non-EBOV isolates tested. The conditions used by Xpert® Ebola for inactivation of infectious virus reduced EBOV titer by ≥6 logs. In conclusion, we found the Xpert® Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection is critical.« less

  17. Analytical Performance Characteristics of the Cepheid GeneXpert Ebola Assay for the Detection of Ebola Virus

    SciTech Connect

    Pinsky, Benjamin A.; Sahoo, Malaya K.; Sandlund, Johanna; Kleman, Marika; Kulkarni, Medha; Grufman, Per; Nygren, Malin; Kwiatkowski, Robert; Baron, Ellen Jo; Tenover, Fred; Denison, Blake; Higuchi, Russell; Van Atta, Reuel; Beer, Neil Reginald; Carrillo, Alda Celena; Naraghi-Arani, Pejman; Mire, Chad E.; Ranadheera, Charlene; Grolla, Allen; Lagerqvist, Nina; Persing, David H.

    2015-11-12

    The recently developed Xpert® Ebola Assay is a novel nucleic acid amplification test for simplified detection of Ebola virus (EBOV) in whole blood and buccal swab samples. The assay targets sequences in two EBOV genes, lowering the risk for new variants to escape detection in the test. The objective of this report is to present analytical characteristics of the Xpert® Ebola Assay on whole blood samples. Our study evaluated the assay’s analytical sensitivity, analytical specificity, inclusivity and exclusivity performance in whole blood specimens. EBOV RNA, inactivated EBOV, and infectious EBOV were used as targets. The dynamic range of the assay, the inactivation of virus, and specimen stability were also evaluated. The lower limit of detection (LoD) for the assay using inactivated virus was estimated to be 73 copies/mL (95% CI: 51–97 copies/mL). The LoD for infectious virus was estimated to be 1 plaque-forming unit/mL, and for RNA to be 232 copies/mL (95% CI 163–302 copies/mL). The assay correctly identified five different Ebola viruses, Yambuku-Mayinga, Makona-C07, Yambuku-Ecran, Gabon-Ilembe, and Kikwit-956210, and correctly excluded all non-EBOV isolates tested. The conditions used by Xpert® Ebola for inactivation of infectious virus reduced EBOV titer by ≥6 logs. In conclusion, we found the Xpert® Ebola Assay to have high analytical sensitivity and specificity for the detection of EBOV in whole blood. It offers ease of use, fast turnaround time, and remote monitoring. The test has an efficient viral inactivation protocol, fulfills inclusivity and exclusivity criteria, and has specimen stability characteristics consistent with the need for decentralized testing. The simplicity of the assay should enable testing in a wide variety of laboratory settings, including remote laboratories that are not capable of performing highly complex nucleic acid amplification tests, and during outbreaks where time to detection is critical.

  18. SSRL HEADLINES March 2009

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    9 March, 2009 __________________________________________________________________________ Contents of this Issue: Science Highlight - Scientists Identify Achilles' Heel of Flu Viruses Science Highlight - Macroscopic Quantum Insulator State Observed SLAC to Receive $68.3 Million in Recovery Act Funding SSRL's New CAMS Group has Great Chemistry XAS Experiments Resume on the 'New' BL4-1 SLAC Shines in Condensed Matter Physics at the March APS Meeting New Alloys under Pressure Studied by Photon

  19. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect

    Lerch, Thomas F.; Chapman, Michael S.

    2012-02-05

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  20. Identification of the heparin binding site on adeno-associated virus serotype 3B (AAV-3B)

    SciTech Connect

    Lerch, Thomas F.; Chapman, Michael S.

    2012-05-24

    Adeno-associated virus is a promising vector for gene therapy. In the current study, the binding site on AAV serotype 3B for the heparan sulfate proteoglycan (HSPG) receptor has been characterized. X-ray diffraction identified a disaccharide binding site at the most positively charged region on the virus surface. The contributions of basic amino acids at this and other sites were characterized using site-directed mutagenesis. Both heparin and cell binding are correlated to positive charge at the disaccharide binding site, and transduction is significantly decreased in AAV-3B vectors mutated at this site to reduce heparin binding. While the receptor attachment sites of AAV-3B and AAV-2 are both in the general vicinity of the viral spikes, the exact amino acids that participate in electrostatic interactions are distinct. Diversity in the mechanisms of cell attachment by AAV serotypes will be an important consideration for the rational design of improved gene therapy vectors.

  1. Towards understanding of Nipah virus attachment protein assembly and the role of protein affinity and crowding for membrane curvature events.

    SciTech Connect

    Stachowiak, Jeanne C.; Hayden, Carl C.; Negrete, Oscar A.; Davis, Ryan Wesley; Sasaki, Darryl Yoshio

    2013-10-01

    Pathogenic viruses are a primary threat to our national security and to the health and economy of our world. Effective defense strategies to combat viral infection and spread require the development of understanding of the mechanisms that these pathogens use to invade the host cell. We present in this report results of our research into viral particle recognition and fusion to cell membranes and the role that protein affinity and confinement in lipid domains plays in membrane curvature in cellular fusion and fission events. Herein, we describe 1) the assembly of the G attachment protein of Nipah virus using point mutation studies to define its role in viral particle fusion to the cell membrane, 2) how lateral pressure of membrane bound proteins induce curvature in model membrane systems, and 3) the role of membrane curvature in the selective partitioning of molecular receptors and specific affinity of associated proteins.

  2. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

    SciTech Connect

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn; Tajima, Shigeru; Hikono, Hirokazu; Saito, Takehiko; Aida, Yoko

    2014-07-18

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC{sub 50} values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets.

  3. The Chlorella variabilis NC64A Genome Reveals Adaptation to Photosymbiosis, Coevolution with Viruses, and Cryptic Sex

    SciTech Connect

    Blanc, Guillaume; Duncan, Garry A.; Agarakova, Irina; Borodovsky, Mark; Gurnon, James; Kuo, Alan; Lindquist, Erika; Lucas, Susan; Pangailinan, Jasmyn; Polle, Juergen; Salamov, Asaf; Terry, Astrid; Yamada, Takashi; Dunigan, David D.; Grigoriev, Igor V.; Claverie, Jean-Michel; Etten, James L. Van

    2010-05-06

    Chlorella variabilis NC64A, a unicellular photosynthetic green alga (Trebouxiophyceae), is an intracellular photobiont of Paramecium bursaria and a model system for studying virus/algal interactions. We sequenced its 46-Mb nuclear genome, revealing an expansion of protein families that could have participated in adaptation to symbiosis. NC64A exhibits variations in GC content across its genome that correlate with global expression level, average intron size, and codon usage bias. Although Chlorella species have been assumed to be asexual and nonmotile, the NC64A genome encodes all the known meiosis-specific proteins and a subset of proteins found in flagella. We hypothesize that Chlorella might have retained a flagella-derived structure that could be involved in sexual reproduction. Furthermore, a survey of phytohormone pathways in chlorophyte algae identified algal orthologs of Arabidopsis thaliana genes involved in hormone biosynthesis and signaling, suggesting that these functions were established prior to the evolution of land plants. We show that the ability of Chlorella to produce chitinous cell walls likely resulted from the capture of metabolic genes by horizontal gene transfer from algal viruses, prokaryotes, or fungi. Analysis of the NC64A genome substantially advances our understanding of the green lineage evolution, including the genomic interplay with viruses and symbiosis between eukaryotes.

  4. Characterization of Coffee ringspot virus-Lavras: A model for an emerging threat to coffee production and quality

    SciTech Connect

    Ramalho, T.O.; Figueira, A.R.; Sotero, A.J.; Wang, R.; Geraldino Duarte, P.S.; Farman, M.; Goodin, M.M.

    2014-09-15

    The emergence of viruses in Coffee (Coffea arabica and Coffea canephora), the most widely traded agricultural commodity in the world, is of critical concern. The RNA1 (6552 nt) of Coffee ringspot virus is organized into five open reading frames (ORFs) capable of encoding the viral nucleocapsid (ORF1p), phosphoprotein (ORF2p), putative cell-to-cell movement protein (ORF3p), matrix protein (ORF4p) and glycoprotein (ORF5p). Each ORF is separated by a conserved intergenic junction. RNA2 (5945 nt), which completes the bipartite genome, encodes a single protein (ORF6p) with homology to RNA-dependent RNA polymerases. Phylogenetic analysis of L protein sequences firmly establishes CoRSV as a member of the recently proposed Dichorhavirus genus. Predictive algorithms, in planta protein expression, and a yeast-based nuclear import assay were used to determine the nucleophillic character of five CoRSV proteins. Finally, the temperature-dependent ability of CoRSV to establish systemic infections in an initially local lesion host was quantified. - Highlights: • We report genome sequence determination for Coffee ringspot virus (CoRSV). • CoRSV should be considered a member of the proposed Dichorhavirus genus. • We report temperature-dependent systemic infection of an initially local lesion host. • We report in planta protein and localization data for five CoRSV proteins. • In silico predictions of the CoRSV proteins were validated using in vivo assays.

  5. Development of a reverse genetics system to generate a recombinant Ebola virus Makona expressing a green fluorescent protein

    SciTech Connect

    Albariño, César G. Wiggleton Guerrero, Lisa; Lo, Michael K.; Nichol, Stuart T.; Towner, Jonathan S.

    2015-10-15

    Previous studies have demonstrated the potential application of reverse genetics technology in studying a broad range of aspects of viral biology, including gene regulation, protein function, cell entry, and pathogenesis. Here, we describe a highly efficient reverse genetics system used to generate recombinant Ebola virus (EBOV) based on a recent isolate from a human patient infected during the 2014–2015 outbreak in Western Africa. We also rescued a recombinant EBOV expressing a fluorescent reporter protein from a cleaved VP40 protein fusion. Using this virus and an inexpensive method to quantitate the expression of the foreign gene, we demonstrate its potential usefulness as a tool for screening antiviral compounds and measuring neutralizing antibodies. - Highlights: • Recombinant Ebola virus (EBOV) derived from Makona variant was rescued. • New protocol for viral rescue allows 100% efficiency. • Modified EBOV expresses a green fluorescent protein from a VP40-fused protein. • Modified EBOV was tested as tool to screen antiviral compounds and measure neutralizing antibodies.

  6. Structural determination of importin alpha in complex with beak and feather disease virus capsid nuclear localization signal

    SciTech Connect

    Patterson, Edward I.; Dombrovski, Andrew K.; Swarbrick, Crystall M.D.; Raidal, Shane R.; Forwood, Jade K.

    2013-09-06

    Highlights: •Circovirus capsid proteins contain large nuclear localization signals (NLS). •A method of nuclear import has not been elucidated. •Beak and feather disease virus (BFDV) capsid NLS was crystallized with importin α. •The structure showed BFDV NLS binding to the major site of importin α. •Result shows implications for mechanism of nuclear transport for all circoviruses. -- Abstract: Circoviruses represent a rapidly increasing genus of viruses that infect a variety of vertebrates. Replication requires shuttling viral molecules into the host cell nucleus, a process facilitated by capsid-associated protein (Cap). Whilst a nuclear localization signal (NLS) has been shown to mediate nuclear translocation, the mode of nuclear transport remains to be elucidated. To better understand this process, beak and feather disease virus (BFDV) Cap NLS was crystallized with nuclear import receptor importin-α (Impα). Diffraction yielded structural data to 2.9 Å resolution, and the binding site on both Impα and BFDV Cap NLS were well resolved. The binding mechanism for the major site is likely conserved across circoviruses as supported by the similarity of NLSs in circovirus Caps. This finding illuminates a crucial step for infection of host cells by this viral family, and provides a platform for rational drug design against the binding interface.

  7. Structure of unliganded HSV gD reveals a mechanism for receptor-mediated activation of virus entry

    SciTech Connect

    Krummenacher, Claude; Supekar, Vinit M.; Whitbeck, J. Charles; Lazear, Eric; Connolly, Sarah A.; Eisenberg, Roselyn J.; Cohen, Gary H.; Wiley, Don C.; Carfi, Andrea

    2010-07-19

    Herpes simplex virus (HSV) entry into cells requires binding of the envelope glycoprotein D (gD) to one of several cell surface receptors. The 50 C-terminal residues of the gD ectodomain are essential for virus entry, but not for receptor binding. We have determined the structure of an unliganded gD molecule that includes these C-terminal residues. The structure reveals that the C-terminus is anchored near the N-terminal region and masks receptor-binding sites. Locking the C-terminus in the position observed in the crystals by an intramolecular disulfide bond abolished receptor binding and virus entry, demonstrating that this region of gD moves upon receptor binding. Similarly, a point mutant that would destabilize the C-terminus structure was nonfunctional for entry, despite increased affinity for receptors. We propose that a controlled displacement of the gD C-terminus upon receptor binding is an essential feature of HSV entry, ensuring the timely activation of membrane fusion.

  8. Rational design and adaptive management of combination therapies for Hepatitis C virus infection

    DOE PAGES [OSTI]

    Ke, Ruian; Loverdo, Claude; Qi, Hangfei; Sun, Ren; Lloyd-Smith, James O.; Kouyos, Roger Dimitri

    2015-06-30

    Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensatemore » when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.« less

  9. Molecular basis of endosomal-membrane association for the dengue virus envelope protein

    DOE PAGES [OSTI]

    Rogers, David M.; Kent, Michael S.; Rempe, Susan B.

    2015-01-02

    Dengue virus is coated by an icosahedral shell of 90 envelope protein dimers that convert to trimers at low pH and promote fusion of its membrane with the membrane of the host endosome. We provide the first estimates for the free energy barrier and minimum for two key steps in this process: host membrane bending and protein–membrane binding. Both are studied using complementary membrane elastic, continuum electrostatics and all-atom molecular dynamics simulations. The predicted host membrane bending required to form an initial fusion stalk presents a 22–30 kcal/mol free energy barrier according to a constrained membrane elastic model. Combined continuummore »and molecular dynamics results predict a 15 kcal/mol free energy decrease on binding of each trimer of dengue envelope protein to a membrane with 30% anionic phosphatidylglycerol lipid. The bending cost depends on the preferred curvature of the lipids composing the host membrane leaflets, while the free energy gained for protein binding depends on the surface charge density of the host membrane. The fusion loop of the envelope protein inserts exactly at the level of the interface between the membrane's hydrophobic and head-group regions. As a result, the methods used in this work provide a means for further characterization of the structures and free energies of protein-assisted membrane fusion.« less

  10. Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20

    SciTech Connect

    McCraw, Dustin M.; O' Donnell, Jason K.; Taylor, Kenneth A.; Stagg, Scott M.; Department of Chemistry and Biochemistry, Florida State University, Tallahassee, FL 32306 ; Chapman, Michael S.

    2012-09-15

    The use of adeno-associated virus (AAV) as a gene therapy vector is limited by the host neutralizing immune response. The cryo-electron microscopy (EM) structure at 8.5 A resolution is determined for a complex of AAV-2 with the Fab' fragment of monoclonal antibody (MAb) A20, the most extensively characterized AAV MAb. The binding footprint is determined through fitting the cryo-EM reconstruction with a homology model following sequencing of the variable domain, and provides a structural basis for integrating diverse prior epitope mappings. The footprint extends from the previously implicated plateau to the side of the spike, and into the conserved canyon, covering a larger area than anticipated. Comparison with structures of binding and non-binding serotypes indicates that recognition depends on a combination of subtle serotype-specific features. Separation of the neutralizing epitope from the heparan sulfate cell attachment site encourages attempts to develop immune-resistant vectors that can still bind to target cells.

  11. Solution Properties of Murine Leukemia Virus Gag Protein: Differences from HIV-1 Gag

    SciTech Connect

    Datta, Siddhartha A.K.; Zuo, Xiaobing; Clark, Patrick K.; Campbell, Stephen J.; Wang, Yun-Xing; Rein, Alan

    2012-05-09

    Immature retrovirus particles are assembled from the multidomain Gag protein. In these particles, the Gag proteins are arranged radially as elongated rods. We have previously characterized the properties of HIV-1 Gag in solution. In the absence of nucleic acid, HIV-1 Gag displays moderately weak interprotein interactions, existing in monomer-dimer equilibrium. Neutron scattering and hydrodynamic studies suggest that the protein is compact, and biochemical studies indicate that the two ends can approach close in three-dimensional space, implying the need for a significant conformational change during assembly. We now describe the properties of the Gag protein of Moloney murine leukemia virus (MLV), a gammaretrovirus. We found that this protein is very different from HIV-1 Gag: it has much weaker protein-protein interaction and is predominantly monomeric in solution. This has allowed us to study the protein by small-angle X-ray scattering and to build a low-resolution molecular envelope for the protein. We found that MLV Gag is extended in solution, with an axial ratio of {approx}7, comparable to its dimensions in immature particles. Mutational analysis suggests that runs of prolines in its matrix and p12 domains and the highly charged stretch at the C terminus of its capsid domain all contribute to this extended conformation. These differences between MLV Gag and HIV-1 Gag and their implications for retroviral assembly are discussed.

  12. A zebrafish (Danio rerio) model of infectious spleen and kidney necrosis virus (ISKNV) infection

    SciTech Connect

    Xu Xiaopeng; Zhang Lichun; Weng Shaoping; Huang Zhijian; Lu Jing; Lan Dongming; Zhong Xuejun; Yu Xiaoqiang; Xu Anlong He Jianguo

    2008-06-20

    Zebrafish is a model animal for studies of genetics, development, toxicology, oncology, and immunology. In this study, infectious spleen and kidney necrosis virus (ISKNV) was used to establish an infection in zebrafish, and the experimental conditions were established and characterized. Mortality of adult zebrafish infected with ISKNV by intraperitoneal (i.p.) injection exceeded 60%. ISKNV can be passed stably in zebrafish for over ten passages. The ailing zebrafish displayed petechial hemorrhaging and scale protrusion. Histological analysis of moribund fish revealed necrosis of tissue and enlarged cells in kidney and spleen. The real-time RT-PCR analysis of mRNA level confirmed that ISKNV was replicated in zebrafish. Immunohistochemistry and immunofluorescence analyses further confirmed the presence of ISKNV-infected cells in almost all organs of the infected fish. Electron microscope analyses showed that the ISKNV particle was present in the infected tissues. The establishment of zebrafish infection model of ISKNV can offer a valuable tool for studying the interactions between ISKNV and its host.

  13. 1D and 2D Assembly of Plant Viruses for Materials Development

    SciTech Connect

    Qian Wang

    2013-01-11

    The research focused on the development of novel bionanoparticle (BNP)-based materials, especially the assembly of chemically and genetically-tailored BNP at the interface between immiscible fluids. The chemical, physical, dynamical and mechanistic aspects have been studied in this research. In particular, rod-like tobacco mosaic virus (TMV) based anisotropic nanorods were synthesized via RNA or polymer assisted assembling process. Such kind of TMV-rods offers an ideal model system for the mechanistic study of orienting and packing anisotropic nanoparticles, which may have great potential in the applications of photovoltaic and field emission devices. Specific objectives include: 1) Synthesize BNPs with controlled functionality at defined positions; 2) synthesize 1D nanorods with defined length via polymer or RNA assisted assembly of TMV or TMV coat proteins; 3) self-assemble and crosslink BNPs and TMV-nanorods at liquid-liquid interfaces; 4) quantitatively characterize the structural organization of the 1D and 2D BNP-assemblies using both small angle neutron scattering and synchrotron small angle X-ray scattering; and 5) develop methods to apply grazing incidence small angle X-ray/neutron scattering to investigate the assemblies of BNPs.

  14. Primary Radiation Therapy for Head-and-Neck Cancer in the Setting of Human Immunodeficiency Virus

    SciTech Connect

    Klein, Emily A.; Guiou, Michael; Farwell, D. Gregory; Luu, Quang; Lau, Derick H.; Stuart, Kerri; Vaughan, Andrew; Vijayakumar, Srinivasan; Chen, Allen M.

    2011-01-01

    Purpose: To analyze outcomes after radiation therapy for head-and-neck cancer among a cohort of patients with human immunodeficiency virus (HIV). Methods and Materials: The medical records of 12 patients with serologic evidence of HIV who subsequently underwent radiation therapy to a median dose of 68 Gy (range, 64-72 Gy) for newly diagnosed squamous cell carcinoma of the head and neck were reviewed. Six patients (50%) received concurrent chemotherapy. Intensity-modulated radiotherapy was used in 6 cases (50%). All patients had a Karnofsky performance status of 80 or 90. Nine patients (75%) were receiving antiretroviral therapies at the time of treatment, and the median CD4 count was 460 (range, 266-800). Toxicity was graded according to the Radiation Therapy Oncology Group / European Organization for the Treatment of Cancer toxicity criteria. Results: The 3-year estimates of overall survival and local-regional control were 78% and 92%, respectively. Acute Grade 3+ toxicity occurred in 7 patients (58%), the most common being confluent mucositis (5 patients) and moist skin desquamation (4 patients). Two patients experienced greater than 10% weight loss, and none experienced more than 15% weight loss from baseline. Five patients (42%) experienced treatment breaks in excess of 10 cumulative days, although none required hospitalization. There were no treatment-related fatalities. Conclusions: Radiation therapy for head-and-neck cancer seems to be relatively well tolerated among appropriately selected patients with HIV. The observed rates of toxicity were comparable to historical controls without HIV.

  15. Molecular basis of endosomal-membrane association for the dengue virus envelope protein

    SciTech Connect

    Rogers, David M.; Kent, Michael S.; Rempe, Susan B.

    2015-01-02

    Dengue virus is coated by an icosahedral shell of 90 envelope protein dimers that convert to trimers at low pH and promote fusion of its membrane with the membrane of the host endosome. We provide the first estimates for the free energy barrier and minimum for two key steps in this process: host membrane bending and protein–membrane binding. Both are studied using complementary membrane elastic, continuum electrostatics and all-atom molecular dynamics simulations. The predicted host membrane bending required to form an initial fusion stalk presents a 22–30 kcal/mol free energy barrier according to a constrained membrane elastic model. Combined continuum and molecular dynamics results predict a 15 kcal/mol free energy decrease on binding of each trimer of dengue envelope protein to a membrane with 30% anionic phosphatidylglycerol lipid. The bending cost depends on the preferred curvature of the lipids composing the host membrane leaflets, while the free energy gained for protein binding depends on the surface charge density of the host membrane. The fusion loop of the envelope protein inserts exactly at the level of the interface between the membrane's hydrophobic and head-group regions. As a result, the methods used in this work provide a means for further characterization of the structures and free energies of protein-assisted membrane fusion.

  16. Protein arginine methyltransferase 1 regulates herpes simplex virus replication through ICP27 RGG-box methylation

    SciTech Connect

    Yu, Jungeun; Shin, Bongjin; Park, Eui-Soon; Yang, Sujeong; Choi, Seunga; Kang, Misun; Rho, Jaerang

    2010-01-01

    Protein arginine methylation is involved in viral infection and replication through the modulation of diverse cellular processes including RNA metabolism, cytokine signaling, and subcellular localization. It has been suggested previously that the protein arginine methylation of the RGG-box of ICP27 is required for herpes simplex virus type-1 (HSV-1) viral replication and gene expression in vivo. However, a cellular mediator for this process has not yet been identified. In our current study, we show that the protein arginine methyltransferase 1 (PRMT1) is a cellular mediator of the arginine methylation of ICP27 RGG-box. We generated arginine substitution mutants in this domain and examined which arginine residues are required for methylation by PRMT1. R138, R148 and R150 were found to be the major sites of this methylation but additional arginine residues serving as minor methylation sites are still required to sustain the fully methylated form of ICP27 RGG. We also demonstrate that the nuclear foci-like structure formation, SRPK interactions, and RNA-binding activity of ICP27 are modulated by the arginine methylation of the ICP27 RGG-box. Furthermore, HSV-1 replication is inhibited by hypomethylation of this domain resulting from the use of general PRMT inhibitors or arginine mutations. Our data thus suggest that the PRMT1 plays a key role as a cellular regulator of HSV-1 replication through ICP27 RGG-box methylation.

  17. Human borna disease virus infection impacts host proteome and histone lysine acetylation in human oligodendroglia cells

    SciTech Connect

    Liu, Xia; Zhao, Libo; Yang, Yongtao; Bode, Liv; Huang, Hua; Liu, Chengyu; Huang, Rongzhong; Zhang, Liang; and others

    2014-09-15

    Background: Borna disease virus (BDV) replicates in the nucleus and establishes persistent infections in mammalian hosts. A human BDV strain was used to address the first time, how BDV infection impacts the proteome and histone lysine acetylation (Kac) of human oligodendroglial (OL) cells, thus allowing a better understanding of infection-driven pathophysiology in vitro. Methods: Proteome and histone lysine acetylation were profiled through stable isotope labeling for cell culture (SILAC)-based quantitative proteomics. The quantifiable proteome was annotated using bioinformatics. Histone acetylation changes were validated by biochemistry assays. Results: Post BDV infection, 4383 quantifiable differential proteins were identified and functionally annotated to metabolism pathways, immune response, DNA replication, DNA repair, and transcriptional regulation. Sixteen of the thirty identified Kac sites in core histones presented altered acetylation levels post infection. Conclusions: BDV infection using a human strain impacted the whole proteome and histone lysine acetylation in OL cells. - Highlights: • A human strain of BDV (BDV Hu-H1) was used to infect human oligodendroglial cells (OL cells). • This study is the first to reveal the host proteomic and histone Kac profiles in BDV-infected OL cells. • BDV infection affected the expression of many transcription factors and several HATs and HDACs.

  18. Nuclear sensing of viral DNA, epigenetic regulation of herpes simplex virus infection, and innate immunity

    SciTech Connect

    Knipe, David M.

    2015-05-15

    Herpes simplex virus (HSV) undergoes a lytic infection in epithelial cells and a latent infection in neuronal cells, and epigenetic mechanisms play a major role in the differential gene expression under the two conditions. HSV viron DNA is not associated with histones but is rapidly loaded with heterochromatin upon entry into the cell. Viral proteins promote reversal of the epigenetic silencing in epithelial cells while the viral latency-associated transcript promotes additional heterochromatin in neuronal cells. The cellular sensors that initiate the chromatinization of foreign DNA have not been fully defined. IFI16 and cGAS are both essential for innate sensing of HSV DNA, and new evidence shows how they work together to initiate innate signaling. IFI16 also plays a role in the heterochromatinization of HSV DNA, and this review will examine how IFI16 integrates epigenetic regulation and innate sensing of foreign viral DNA to show how these two responses are related. - Highlights: • HSV lytic and latent gene expression is regulated differentially by epigenetic processes. • The sensors of foreign DNA have not been defined fully. • IFI16 and cGAS cooperate to sense viral DNA in HSV-infected cells. • IFI16 plays a role in both innate sensing of HSV DNA and in restricting its expression.

  19. Interaction between human BAP31 and respiratory syncytial virus small hydrophobic (SH) protein

    SciTech Connect

    Li, Yan; Jain, Neeraj; Limpanawat, Suweeraya; To, Janet; Quistgaard, Esben M.; Nordlund, Par; Thanabalu, Thirumaran; Torres, Jaume

    2015-08-15

    The small hydrophobic (SH) protein is a short channel-forming polypeptide encoded by the human respiratory syncytial virus (hRSV). Deletion of SH protein leads to the viral attenuation in mice and primates, and delayed apoptosis in infected cells. We have used a membrane-based yeast two-hybrid system (MbY2H) and a library from human lung cDNA to detect proteins that bind SH protein. This led to the identification of a membrane protein, B-cell associated protein 31 (BAP31). Transfected SH protein co-localizes with transfected BAP31 in cells, and pulls down endogenous BAP31. Titration of purified C-terminal endodomain of BAP31 against isotopically labeled SH protein in detergent micelles suggests direct interaction between the two proteins. Given the key role of BAP31 in protein trafficking and its critical involvement in pro- and anti-apoptotic pathways, this novel interaction may constitute a potential drug target. - Highlights: • A yeast two-hybrid system (MbY2H) detected BAP31 as a binder of RSV SH protein. • Transfected SH and BAP31 co-localize in lung epithelial cells. • Endogenous BAP31 is pulled down by RSV SH protein. • BAP31 endodomain interacts with the N-terminal α-helix of SH protein in micelles. • This interaction is proposed to be a potential drug target.

  20. The cowpox virus fusion regulator proteins SPI-3 and hemagglutinin interact in infected and uninfected cells

    SciTech Connect

    Turner, Peter C. . E-mail: rmoyer@ufl.edu

    2006-03-30

    The serpin SPI-3 and the hemagglutinin (HA) encoded by cowpox virus (CPV) block cell-cell fusion, and colocalize at the cell surface. wtCPV does not fuse cells, but inactivation of either gene leads to fusion. SPI-3 mAb added to wtCPV-infected cells caused fusion, confirming that SPI-3 protein at the cell surface prevents fusion. The SPI-3 mAb epitope mapped to an 85-amino acid region at the C-terminus. Removal of either 44 residues from the SPI-3 C-terminus or 48 residues following the N-terminal signal sequence resulted in fusion. Interaction between SPI-3 and HA proteins in infected cells was shown by coimmunoprecipitation. SPI-3/HA was not associated with the A27L 'fusion' protein. SPI-3 and HA were able to associate in uninfected cells in the absence of other viral proteins. The HA-binding domain in SPI-3 resided in the C-terminal 229 residues, and did not include helix D, which mediates cofactor interaction in many other serpins.

  1. Rational design and adaptive management of combination therapies for Hepatitis C virus infection

    SciTech Connect

    Ke, Ruian; Loverdo, Claude; Qi, Hangfei; Sun, Ren; Lloyd-Smith, James O.; Kouyos, Roger Dimitri

    2015-06-30

    Recent discoveries of direct acting antivirals against Hepatitis C virus (HCV) have raised hopes of effective treatment via combination therapies. Yet rapid evolution and high diversity of HCV populations, combined with the reality of suboptimal treatment adherence, make drug resistance a clinical and public health concern. We develop a general model incorporating viral dynamics and pharmacokinetics/ pharmacodynamics to assess how suboptimal adherence affects resistance development and clinical outcomes. We derive design principles and adaptive treatment strategies, identifying a high-risk period when missing doses is particularly risky for de novo resistance, and quantifying the number of additional doses needed to compensate when doses are missed. Using data from large-scale resistance assays, we demonstrate that the risk of resistance can be reduced substantially by applying these principles to a combination therapy of daclatasvir and asunaprevir. By providing a mechanistic framework to link patient characteristics to the risk of resistance, these findings show the potential of rational treatment design.

  2. Human immunodeficiency virus contains an epitope immunoreactive with thymosin. cap alpha. /sub 1/ and the 30-amino acid synthetic p17 group-specific antigen peptide HGP-30

    SciTech Connect

    Naylor, P.H.; Naylor, C.W.; Badamchian, M.; Wada, S.; Goldstein, A.L.; Wang, S.S.; Sun, D.K.; Thornton, A.H.; Sarin, P.S.

    1987-05-01

    The authors have reported that an antiserum prepared against thymosin ..cap alpha../sub 1/ (which shares a region of homology with the p17 protein of the acquired immunodeficiency syndrome (AIDS)-associated human immunodeficiency virus) effectively neutralized the AIDs virus and prevented its replication in H9 cells. Using HPLC and immunoblot analysis, they have identified from a clone B, type III human T-lymphotropic virus (HTLV-IIIB) extracts a protein with a molecular weight of 17,000 that is immunoreactive with thymosin ..cap alpha../sub 1/. In contrast, no immunoreactivity was found in retroviral extracts from a number of nonhuman species including feline, bovine, simian, gibbon, and murine retroviruses. Heterologous antiserum prepared against a 30-amino acid synthetic peptide analogue (HGP-30) does not cross-react with thymosin ..cap alpha../sub 1/ but does react specifically with the p17 protein of the AIDS virus in a manner identical to that seen with an HTLV-IIIB p17-specific monoclonal antibody. The demonstration that this synthetic analogue is immunogenic and that antibodies to HGP-30 cross-react not only with synthetic peptide but also with the HTLV-IIIB p17 viral protein provides an additional, and potentially more specific, candidate for development of a synthetic peptide vaccine for AIDS. In addition, the p17 synthetic peptide (HGP-3) may prove to be useful in a diagnostic assay for the detection of AIDS virus infection in seronegative individuals.

  3. Canine distemper virus neutralization activity is low in human serum and it is sensitive to an amino acid substitution in the hemagglutinin protein

    SciTech Connect

    Zhang, Xinsheng; Wallace, Olivia L.; Domi, Arban; Wright, Kevin J.; Driscoll, Jonathan; Anzala, Omu; Sanders, Eduard J.; Kamali, Anatoli; Allen, Susan; Fast, Pat; Gilmour, Jill; Price, Matt A.; Parks, Christopher L.

    2015-08-15

    Serum was analyzed from 146 healthy adult volunteers in eastern Africa to evaluate measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb) prevalence and potency. MV plaque reduction neutralization test (PRNT) results indicated that all sera were positive for MV nAbs. Furthermore, the 50% neutralizing dose (ND50) for the majority of sera corresponded to antibody titers induced by MV vaccination. CDV nAbs titers were low and generally were detected in sera with high MV nAb titers. A mutant CDV was generated that was less sensitive to neutralization by human serum. The mutant virus genome had 10 nucleotide substitutions, which coded for single amino acid substitutions in the fusion (F) and hemagglutinin (H) glycoproteins and two substitutions in the large polymerase (L) protein. The H substitution occurred in a conserved region involved in receptor interactions among morbilliviruses, implying that this region is a target for cross-reactive neutralizing antibodies. - Highlights: • Screened 146 serum samples for measles virus (MV) and canine distemper virus (CDV) neutralizing antibody (nAb). • MV nAb is prevalent in the sera. • CDV neutralizing activity is generally low or absent and when detected it is present in sera with high MV nAb titers. • A neutralization-resistant CDV mutant was isolated using human serum selection. • A mutation was identified in the receptor-binding region of CDV hemagglutinin protein that confers the neutralization resistance.

  4. Protection from the toxicity of diisopropylfluorophosphate by adeno-associated virus expressing acetylcholinesterase

    SciTech Connect

    Li Bin; Duysen, Ellen G.; Poluektova, Larisa Y.; Murrin, L. Charles . E-mail: cmurrin@unmc.edu; Lockridge, Oksana . E-mail: olockrid@unmc.edu

    2006-07-15

    Organophosphorus esters (OP) are highly toxic chemicals used as pesticides and nerve agents. Their acute toxicity is attributed to inhibition of acetylcholinesterase (AChE, EC 3.1.1.7) in nerve synapses. Our goal was to find a new therapeutic for protection against OP toxicity. We used a gene therapy vector, adeno-associated virus serotype 2 (AAV-2), to deliver murine AChE to AChE-/- mice that have no endogenous AChE activity. The vector encoded the most abundant form of AChE: exons 2, 3, 4, and 6. Two-day old animals, with an immature immune system, were injected. AChE delivered intravenously was expressed up to 5 months in plasma, liver, heart, and lung, at 5-15% of the level in untreated wild-type mice. A few mice formed antibodies, but antibodies did not block AChE activity. The plasma AChE was a mixture of dimers and tetramers. AChE delivered intramuscularly had 40-fold higher activity levels than in wild-type muscle. None of the AChE was collagen-tailed. No retrograde transport through the motor neurons to the central nervous system was detected. AChE delivered intrastriatally assembled into tetramers. In brain, the AAV-2 vector transduced neurons, but not astrocytes and microglia. Vector-treated AChE-/- mice lived longer than saline-treated controls. AChE-/- mice were protected from diisopropylfluorophosphate-induced respiratory failure when the vector was delivered intravenously, but not intrastriatally. Since vector-treated animals had no AChE activity in diaphragm muscle, protection from respiratory failure came from AChE in other tissues. We conclude that AChE scavenged OP and in this way protected the activity of butyrylcholinesterase (BChE, EC 3.1.1.8) in motor endplates.

  5. Inhibition of hepatitis B virus (HBV) by LNA-mediated nuclear interference with HBV DNA transcription

    SciTech Connect

    Sun, Zhen; Department of Biochemistry and Molecular Biology, Program in Molecular Cell Biology, Zhejiang University School of Medicine, Hangzhou, Zhejiang 310058 ; Xiang, Wenqing; Guo, Yajuan; Chen, Zhi; Liu, Wei; Lu, Daru

    2011-06-10

    Highlights: {yields} LNA-modified oligonucleotides can pass through the plasma membrane of cultured cells even without using transfection machinery. {yields} LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. {yields} LNA-oligonucleotide designed to target nuclear HBV DNA efficiently suppresses HBV replication and transcription in cultured hepatic cells. -- Abstract: Silencing target genes with small regulatory RNAs is widely used to investigate gene function and therapeutic drug development. Recently, triplex-based approaches have provided another attractive means to achieve targeted gene regulation and gene manipulation at the molecular and cellular levels. Nuclear entry of oligonucleotides and enhancement of their affinity to the DNA targets are key points of such approaches. In this study, we developed lipid-based transport of a locked-nucleic-acid (LNA)-modified oligonucleotide for hepatitis B virus (HBV) DNA interference in human hepatocytes expressing HBV genomic DNA. In these cells, the LNA-modified oligonucleotides passed efficiently across the cell membrane, and lipid-coating facilitated translocation from the cytoplasm to the nucleus. The oligonucleotide specifically targeting HBV DNA clearly interfered with HBV DNA transcription as shown by a block in pregenomic RNA (pgRNA) production. The HBV DNA-targeted oligonucleotide suppressed HBV DNA replication and HBV protein production more efficiently than small interfering RNAs directed to the pgRNA. These results demonstrate that fusion with lipid can carry LNA-modified oligonucleotides to the nucleus where they regulate gene expression. Interfering with HBV DNA transcription by LNA-modified oligonucleotides has strong potential as a new strategy for HBV inhibition.

  6. Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA glycosylase

    SciTech Connect

    Schormann, Norbert; Banerjee, Surajit; Ricciardi, Robert; Chattopadhyay, Debasish

    2015-06-02

    Background: Uracil-DNA glycosylases are evolutionarily conserved DNA repair enzymes. However, vaccinia virus uracil-DNA glycosylase (known as D4), also serves as an intrinsic and essential component of the processive DNA polymerase complex during DNA replication. In this complex D4 binds to a unique poxvirus specific protein A20 which tethers it to the DNA polymerase. At the replication fork the DNA scanning and repair function of D4 is coupled with DNA replication. So far, DNA-binding to D4 has not been structurally characterized. Results: This manuscript describes the first structure of a DNA-complex of a uracil-DNA glycosylase from the poxvirus family. This also represents the first structure of a uracil DNA glycosylase in complex with an undamaged DNA. In the asymmetric unit two D4 subunits bind simultaneously to complementary strands of the DNA double helix. Each D4 subunit interacts mainly with the central region of one strand. DNA binds to the opposite side of the A20-binding surface on D4. In comparison of the present structure with the structure of uracil-containing DNA-bound human uracil-DNA glycosylase suggests that for DNA binding and uracil removal D4 employs a unique set of residues and motifs that are highly conserved within the poxvirus family but different in other organisms. Conclusion: The first structure of D4 bound to a truly non-specific undamaged double-stranded DNA suggests that initial binding of DNA may involve multiple non-specific interactions between the protein and the phosphate backbone.

  7. Binding of undamaged double stranded DNA to vaccinia virus uracil-DNA glycosylase

    DOE PAGES [OSTI]

    Schormann, Norbert; Banerjee, Surajit; Ricciardi, Robert; Chattopadhyay, Debasish

    2015-06-02

    Background: Uracil-DNA glycosylases are evolutionarily conserved DNA repair enzymes. However, vaccinia virus uracil-DNA glycosylase (known as D4), also serves as an intrinsic and essential component of the processive DNA polymerase complex during DNA replication. In this complex D4 binds to a unique poxvirus specific protein A20 which tethers it to the DNA polymerase. At the replication fork the DNA scanning and repair function of D4 is coupled with DNA replication. So far, DNA-binding to D4 has not been structurally characterized. Results: This manuscript describes the first structure of a DNA-complex of a uracil-DNA glycosylase from the poxvirus family. This alsomore » represents the first structure of a uracil DNA glycosylase in complex with an undamaged DNA. In the asymmetric unit two D4 subunits bind simultaneously to complementary strands of the DNA double helix. Each D4 subunit interacts mainly with the central region of one strand. DNA binds to the opposite side of the A20-binding surface on D4. In comparison of the present structure with the structure of uracil-containing DNA-bound human uracil-DNA glycosylase suggests that for DNA binding and uracil removal D4 employs a unique set of residues and motifs that are highly conserved within the poxvirus family but different in other organisms. Conclusion: The first structure of D4 bound to a truly non-specific undamaged double-stranded DNA suggests that initial binding of DNA may involve multiple non-specific interactions between the protein and the phosphate backbone.« less

  8. Both core and F proteins of hepatitis C virus could enhance cell proliferation in transgenic mice

    SciTech Connect

    Hu, Wen-Ta; Li, Hui-Chun; Lee, Shen-Kao; Ma, Hsin-Chieh; Yang, Chee-Hing; Chen, Hung-Ling; Lo, Shih-Yen; Department of Laboratory Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan

    2013-05-24

    Highlights: HCV core and F proteins could induce hepatocyte proliferation in the transgenic mice. ?-Catenin signaling pathway was activated by core protein in the transgenic mice. ?-Catenin signaling pathway was activated by myc-F protein in the transgenic mice. Expression of SMA protein was enhanced by core but not myc-F protein. -- Abstract: The role of the protein encoded by the alternative open reading frame (ARF/F/core+1) of the Hepatitis C virus (HCV) genome in viral pathogenesis remains unknown. The different forms of ARF/F/core+1 protein were labile in cultured cells, a myc-tag fused at the N-terminus of the F protein made it more stable. To determine the role of core and F proteins in HCV pathogenesis, transgenic mice with either protein expression under the control of Albumin promoter were generated. Expression of core protein and F protein with myc tag (myc-F) could be detected by Western blotting analysis in the livers of these mice. The ratio of liver to body weight is increased for both core and myc-F transgenic mice compared to that of wild type mice. Indeed, the proliferating cell nuclear antigen protein, a proliferation marker, was up-regulated in the transgenic mice with core or myc-F protein. Further analyses by microarray and Western blotting suggested that ?-catenin signaling pathway was activated by either core or myc-F protein in the transgenic mice. These transgenic mice were further treated with either Diethynitrosamine (a tumor initiator) or Phenobarbital (a tumor promoter). Phenobarbital but not Diethynitrosamine treatment could increase the liver/body weight ratio of these mice. However, no tumor formation was observed in these mice. In conclusion, HCV core and myc-F proteins could induce hepatocyte proliferation in the transgenic mice possibly through ?-catenin signaling pathway.

  9. The Role of a Host Protein (TIP) in the Resistance Response of Arabidopsis to Turnip Crinkle Virus Infection.

    SciTech Connect

    T. Jack Morris, School of Biological Sciences, University of Nebraska, Lincoln, NE 68588-0118

    2008-10-20

    Our research on Turnip crinkle virus (TCV) has shown that the viral capsid protein (CP) is both a virulence factor as well as the elicitor of a hypersensitive resistance response (HR) to the virus in Arabidopsis. Initially, we identified a protein from Arabidopsis that specifically interacted with the viral CP using a yeast two-hybrid screen. This protein, designated TIP for TCV-Interacting Protein, is a member of the NAC family of plant transcription factors implicated in the regulation of development and senescence. When TCV CP was mutated to eliminate its ability to interact with TIP, the corresponding virus mutants broke the HR-mediated resistance conferred by the HRT resistance (R) gene in Arabidopsis ecotype Dijon (Di)-17. This result suggested that TIP is a component of the signal transduction pathway that leads to the genetically specified TCV resistance. We next confirmed that TIP and the viral CP interact in plant cells and that this interaction prevents nuclear localization of this transcription factor. We demonstrated that TCV CP suppresses post-transcriptional gene silencing (PTGS), a newly discovered RNA-mediated defense system in plants. Together these results suggest that the CP is a virulence factor that could well be functioning through its interaction with TIP. We have proposed a model involving the role of TIP and CP in triggering HR mediated plant defense that fits with the current thinking about how gene-for-gene resistance may function. A unique component of our system is the opportunity to link R-gene function with the newly discovered RNA silencing pathway that is not only a potent defense against viral pathogens, but also regulates early development in plants. In the current funding period we made several significant findings: First, we completed an array analysis comparing gene expression in Arabidopsis infected with TCV and a mutant virus unable to bind TIP. Second, we produced transgenic lines that over-express and inducibly under

  10. Suboptimal inhibition of protease activity in human immunodeficiency virus type 1: Effects on virion morphogenesis and RNA maturation

    SciTech Connect

    Moore, Michael D.; Fu, William; Soheilian, Ferri; Nagashima, Kunio; Ptak, Roger G.; Pathak, Vinay K.; Hu, Wei-Shau

    2008-09-15

    Protease activity within nascently released human immunodeficiency virus type 1 (HIV-1) particles is responsible for the cleavage of the viral polyproteins Gag and Gag-Pol into their constituent parts, which results in the subsequent condensation of the mature conical core surrounding the viral genomic RNA. Concomitant with viral maturation is a conformational change in the packaged viral RNA from a loosely associated dimer into a more thermodynamically stable form. In this study we used suboptimal concentrations of two protease inhibitors, lopinavir and atazanavir, to study their effects on Gag polyprotein processing and on the properties of the RNA in treated virions. Analysis of the treated virions demonstrated that even with high levels of inhibition of viral infectivity (IC{sub 90}), most of the Gag and Gag-Pol polyproteins were processed, although slight but significant increases in processing intermediates of Gag were detected. Drug treatments also caused a significant increase in the proportion of viruses displaying either immature or aberrant mature morphologies. The aberrant mature particles were characterized by an electron-dense region at the viral periphery and an electron-lucent core structure in the viral center, possibly indicating exclusion of the genomic RNA from these viral cores. Intriguingly, drug treatments caused only a slight decrease in overall thermodynamic stability of the viral RNA dimer, suggesting that the dimeric viral RNA was able to mature in the absence of correct core condensation.

  11. Release of the herpes simplex virus 1 protease by self cleavage is required for proper conformation of the portal vertex

    SciTech Connect

    Yang, Kui; Wills, Elizabeth G.; Baines, Joel D.

    2012-07-20

    We identify an NLS within herpes simplex virus scaffold proteins that is required for optimal nuclear import of these proteins into infected or uninfected nuclei, and is sufficient to mediate nuclear import of GFP. A virus lacking this NLS replicated to titers reduced by 1000-fold, but was able to make capsids containing both scaffold and portal proteins suggesting that other functions can complement the NLS in infected cells. We also show that Vp22a, the major scaffold protein, is sufficient to mediate the incorporation of portal protein into capsids, whereas proper portal immunoreactivity in the capsid requires the larger scaffold protein pU{sub L}26. Finally, capsid angularization in infected cells did not require the HSV-1 protease unless full length pU{sub L}26 was expressed. These data suggest that the HSV-1 portal undergoes conformational changes during capsid maturation, and reveal that full length pU{sub L}26 is required for this conformational change.

  12. Activation/proliferation and apoptosis of bystander goat lymphocytes induced by a macrophage-tropic chimeric caprine arthritis encephalitis virus expressing SIV Nef

    SciTech Connect

    Bouzar, Baya Amel; Rea, Angela; Hoc-Villet, Stephanie; Garnier, Celine; Guiguen, Francois; Jin Yuhuai; Narayan, Opendra; Chebloune, Yahia . E-mail: ychebloune@kumc.edu

    2007-08-01

    Caprine arthritis encephalitis virus (CAEV) is the natural lentivirus of goats, well known for its tropism for macrophages and its inability to cause infection in lymphocytes. The viral genome lacks nef, tat, vpu and vpx coding sequences. To test the hypothesis that when nef is expressed by the viral genome, the virus became toxic for lymphocytes during replication in macrophages, we inserted the SIVsmm PBj14 nef coding sequences into the genome of CAEV thereby generating CAEV-nef. This recombinant virus is not infectious for lymphocytes but is fully replication competent in goat macrophages in which it constitutively expresses the SIV Nef. We found that goat lymphocytes cocultured with CAEV-nef-infected macrophages became activated, showing increased expression of the interleukin-2 receptor (IL-2R). Activation correlated with increased proliferation of the cells. Interestingly, a dual effect in terms of apoptosis regulation was observed in exposed goat lymphocytes. Nef was found first to induce a protection of lymphocytes from apoptosis during the first few days following exposure to infected macrophages, but later it induced increased apoptosis in the activated lymphocytes. This new recombinant virus provides a model to study the functions of Nef in the context of infection of macrophages, but in absence of infection of T lymphocytes and brings new insights into the biological effects of Nef on lymphocytes.

  13. A human monoclonal antibody derived from a vaccinated volunteer recognizes heterosubtypically a novel epitope on the hemagglutinin globular head of H1 and H9 influenza A viruses

    SciTech Connect

    Boonsathorn, Naphatsawan; Panthong, Sumolrat; Chittaganpitch, Malinee; Phuygun, Siripaporn; Waicharoen, Sunthareeya; Prachasupap, Apichai; Yasugi, Mayo; Ono, Ken-ichiro; and others

    2014-09-26

    Highlights: A human monoclonal antibody against influenza virus was produced from a volunteer. The antibody was generated from the PBMCs of the volunteer using the fusion method. The antibody neutralized heterosubtypically group 1 influenza A viruses (H1 and H9). The antibody targeted a novel epitope in globular head region of the hemagglutinin. Sequences of the identified epitope are highly conserved among H1 and H9 subtypes. - Abstract: Most neutralizing antibodies elicited during influenza virus infection or by vaccination have a narrow spectrum because they usually target variable epitopes in the globular head region of hemagglutinin (HA). In this study, we describe a human monoclonal antibody (HuMAb), 5D7, that was prepared from the peripheral blood lymphocytes of a vaccinated volunteer using the fusion method. The HuMAb heterosubtypically neutralizes group 1 influenza A viruses, including seasonal H1N1, 2009 pandemic H1N1 (H1N1pdm) and avian H9N2, with a strong hemagglutinin inhibition activity. Selection of an escape mutant showed that the HuMAb targets a novel conformational epitope that is located in the HA head region but is distinct from the receptor binding site. Furthermore, Phe114Ile substitution in the epitope made the HA unrecognizable by the HuMAb. Amino acid residues in the predicted epitope region are also highly conserved in the HAs of H1N1 and H9N2. The HuMAb reported here may be a potential candidate for the development of therapeutic/prophylactic antibodies against H1 and H9 influenza viruses.

  14. Development and Characterization of A Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out

    SciTech Connect

    Smith, S M; Danganan, L; Tammero, L; Vitalis, B; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed candidate multiplexed assays that may potentially be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the ability to improve our nation's capability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect food and agricultural resources with a diagnostic test which could enhance the nation's capabilities for early detection of a foreign animal disease. In FY2005 with funding from the DHS, LLNL developed the first version (Version 1.0) of a multiplexed (MUX) nucleic-acid-based RT-PCR assay that included signatures for foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases (FADs) of swine, Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease Virus (SVDV), and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus [BPSV], Orf of sheep, and Pseudocowpox). In FY06, LLNL has developed Bovine and Porcine species-specific panel which included existing signatures from Version 1.0 panel as well as new signatures. The MUX RT-PCR porcine assay for detection of FMDV includes the FADs, VESV and SVD in addition to vesicular stomatitis virus (VSV) and porcine reproductive and respiratory syndrome (PRRS). LLNL has also developed a MUX RT-PCR bovine assay for detection of FMDV with rule out tests for the two bovine FADs malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV

  15. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    SciTech Connect

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; Shabman, Reed  S.; Chiu, Wah; Davey, Robert  A.; Otwinowski, Zbyszek; Basler, Christopher  F.; Amarasinghe, Gaya  K.

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludes a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.

  16. Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during SHIV mucosal infection in rhesus macaques

    SciTech Connect

    Santra, Sampa; Tomaras, Georgia D.; Warrier, Ranjit; Nicely, Nathan I.; Liao, Hua -Xin; Pollara, Justin; Liu, Pinghuang; Alam, S. Munir; Zhang, Ruijun; Cocklin, Sarah L.; Shen, Xiaoying; Duffy, Ryan; Xia, Shi -Mao; Schutte, Robert J.; Pemble IV, Charles W.; Dennison, S. Moses; Li, Hui; Chao, Andrew; Vidnovic, Kora; Evans, Abbey; Klein, Katja; Kumar, Amit; Robinson, James; Landucci, Gary; Forthal, Donald N.; Montefiori, David C.; Kaewkungwal, Jaranit; Nitayaphan, Sorachai; Pitisuttithum, Punnee; Rerks-Ngarm, Supachai; Robb, Merlin L.; Michael, Nelson L.; Kim, Jerome H.; Soderberg, Kelly A.; Giorgi, Elena E.; Blair, Lily; Korber, Bette T.; Moog, Christiane; Shattock, Robin J.; Letvin, Norman L.; Schmitz, Joern E.; Moody, M. A.; Gao, Feng; Ferrari, Guido; Shaw, George M.; Haynes, Barton F.; Douek, Daniel C.

    2015-08-03

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4⁺ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant region of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.

  17. Human non-neutralizing HIV-1 envelope monoclonal antibodies limit the number of founder viruses during SHIV mucosal infection in rhesus macaques

    DOE PAGES [OSTI]

    Santra, Sampa; Tomaras, Georgia D.; Warrier, Ranjit; Nicely, Nathan I.; Liao, Hua -Xin; Pollara, Justin; Liu, Pinghuang; Alam, S. Munir; Zhang, Ruijun; Cocklin, Sarah L.; et al

    2015-08-03

    HIV-1 mucosal transmission begins with virus or virus-infected cells moving through mucus across mucosal epithelium to infect CD4⁺ T cells. Although broadly neutralizing antibodies (bnAbs) are the type of HIV-1 antibodies that are most likely protective, they are not induced with current vaccine candidates. In contrast, antibodies that do not neutralize primary HIV-1 strains in the TZM-bl infection assay are readily induced by current vaccine candidates and have also been implicated as secondary correlates of decreased HIV-1 risk in the RV144 vaccine efficacy trial. Here, we have studied the capacity of anti-Env monoclonal antibodies (mAbs) against either the immunodominant regionmore » of gp41 (7B2 IgG1), the first constant region of gp120 (A32 IgG1), or the third variable loop (V3) of gp120 (CH22 IgG1) to modulate in vivo rectal mucosal transmission of a high-dose simian-human immunodeficiency virus (SHIV-BaL) in rhesus macaques. 7B2 IgG1 or A32 IgG1, each containing mutations to enhance Fc function, was administered passively to rhesus macaques but afforded no protection against productive clinical infection while the positive control antibody CH22 IgG1 prevented infection in 4 of 6 animals. Enumeration of transmitted/founder (T/F) viruses revealed that passive infusion of each of the three antibodies significantly reduced the number of T/F genomes. Some antibodies that bind HIV-1 Env but fail to neutralize virus in traditional neutralization assays may limit the number of T/F viruses involved in transmission without leading to enhancement of viral infection. For one of these mAbs, gp41 mAb 7B2, we provide the first co-crystal structure in complex with a common cyclical loop motif demonstrated to be critical for infection by other retroviruses.« less

  18. Structure of the vesicular stomatitis virus nucleocapsid in complex with the nucleocapsid-binding domain of the small polymerase cofactor, P

    SciTech Connect

    Green, Todd J.; Luo, Ming

    2009-10-05

    The negative-strand RNA viruses (NSRVs) are unique because their nucleocapsid, not the naked RNA, is the active template for transcription and replication. The viral polymerase of nonsegmented NSRVs contains a large polymerase catalytic subunit (L) and a nonenzymatic cofactor, the phosphoprotein (P). Insight into how P delivers the polymerase complex to the nucleocapsid has long been pursued by reverse genetics and biochemical approaches. Here, we present the X-ray crystal structure of the C-terminal domain of P of vesicular stomatitis virus, a prototypic nonsegmented NSRV, bound to nucleocapsid-like particles. P binds primarily to the C-terminal lobe of 2 adjacent N proteins within the nucleocapsid. This binding mode is exclusive to the nucleocapsid, not the nucleocapsid (N) protein in other existing forms. Localization of phosphorylation sites within P and their proximity to the RNA cavity give insight into how the L protein might be oriented to access the RNA template.

  19. Development and Characterization of a Multiplexed RT-PCR Species Specific Assay for Bovine and one for Porcine Foot-and-Mouth Disease Virus Rule-Out Supplemental Materials

    SciTech Connect

    Smith, S; Danganan, L; Tammero, L; Lenhoff, R; Naraghi-arani, P; Hindson, B

    2007-08-06

    Lawrence Livermore National Laboratory (LLNL), in collaboration with the Department of Homeland Security (DHS) and the United States Department of Agriculture (USDA), Animal and Plant Health Inspection Services (APHIS) has developed advanced rapid diagnostics that may be used within the National Animal Health Laboratory Network (NAHLN), the National Veterinary Services Laboratory (Ames, Iowa) and the Plum Island Animal Disease Center (PIADC). This effort has the potential to improve our nation's ability to discriminate between foreign animal diseases and those that are endemic using a single assay, thereby increasing our ability to protect animal populations of high economic importance in the United States. Under 2005 DHS funding we have developed multiplexed (MUX) nucleic-acid-based PCR assays that combine foot-and-mouth disease virus (FMDV) detection with rule-out tests for two other foreign animal diseases Vesicular Exanthema of Swine (VESV) and Swine Vesicular Disease (SVD) and four other domestic viral diseases Bovine Viral Diarrhea Virus (BVDV), Bovine Herpes Virus 1 (BHV-1 or Infectious Bovine Rhinotracheitus IBR), Bluetongue virus (BTV) and Parapox virus complex (which includes Bovine Papular Stomatitis Virus BPSV, Orf of sheep, and Pseudocowpox). Under 2006 funding we have developed a Multiplexed PCR [MUX] porcine assay for detection of FMDV with rule out tests for VESV and SVD foreign animal diseases in addition to one other domestic vesicular animal disease vesicular stomatitis virus (VSV) and one domestic animal disease of swine porcine reproductive and respiratory syndrome (PRRS). We have also developed a MUX bovine assay for detection of FMDV with rule out tests for the two bovine foreign animal diseases malignant catarrhal fever (MCF), rinderpest virus (RPV) and the domestic diseases vesicular stomatitis virus (VSV), bovine viral diarrhea virus (BVDV), infectious bovine rhinotracheitus virus (BHV-1), bluetongue virus (BTV), and the Parapox viruses

  20. The coat protein of Alternanthera mosaic virus is the elicitor of a temperature-sensitive systemic necrosis in Nicotiana benthamiana, and interacts with a host boron transporter protein

    SciTech Connect

    Lim, Hyoun-Sub; Nam, Jiryun; Seo, Eun-Young; Nam, Moon; Vaira, Anna Maria; Bae, Hanhong; Jang, Chan-Yong; Lee, Cheol Ho; Kim, Hong Gi; Roh, Mark; Hammond, John

    2014-03-15

    Different isolates of Alternanthera mosaic virus (AltMV; Potexvirus), including four infectious clones derived from AltMV-SP, induce distinct systemic symptoms in Nicotiana benthamiana. Virus accumulation was enhanced at 15 °C compared to 25 °C; severe clone AltMV 3-7 induced systemic necrosis (SN) and plant death at 15 °C. No interaction with potexvirus resistance gene Rx was detected, although SN was ablated by silencing of SGT1, as for other cases of potexvirus-induced necrosis. Substitution of AltMV 3-7 coat protein (CP{sub SP}) with that from AltMV-Po (CP{sub Po}) eliminated SN at 15 °C, and ameliorated symptoms in Alternanthera dentata and soybean. Substitution of only two residues from CP{sub Po} [either MN(13,14)ID or LA(76,77)IS] efficiently ablated SN in N. benthamiana. CP{sub SP} but not CP{sub Po} interacted with Arabidopsis boron transporter protein AtBOR1 by yeast two-hybrid assay; N. benthamiana homolog NbBOR1 interacted more strongly with CP{sub SP} than CP{sub Po} in bimolecular fluorescence complementation, and may affect recognition of CP as an elicitor of SN. - Highlights: • Alternanthera mosaic virus CP is an elicitor of systemic necrosis in N. benthamiana. • Virus-induced systemic necrosis is enhanced at 15 °C compared to 25 °C. • Induction of systemic necrosis is dependent on as few as two CP amino acid residues. • These residues are at subunit interfaces within the same turn of the virion helix. • Inducer/non-inducer CPs interact differentially with a boron transporter protein.

  1. A genome-wide RNA interference screen identifies a role for Wnt/β-catenin signaling during Rift Valley Fever Virus infection

    DOE PAGES [OSTI]

    Harmon, Brooke; Bird, Sara W.; Schudel, Benjamin R.; Hatch, Anson V.; Rasley, Amy; Negrete, Oscar A.

    2016-05-25

    Rift Valley fever virus (RVFV) is an arbovirus within the Bunyaviridae family capable of causing serious morbidity and mortality in humans and livestock. To identify host factors involved in bunyavirus replication, we employed genome-wide RNA interference (RNAi) screening and identified 381 genes whose knockdown reduced infection. The Wnt pathway was the most represented pathway when gene hits were functionally clustered. With further investigation, we found that RVFV infection activated Wnt signaling, was enhanced when Wnt signaling was preactivated, was reduced with knockdown of β-catenin, and was blocked using Wnt signaling inhibitors. Similar results were found using distantly related bunyaviruses Lamore » Crosse virus and California encephalitis virus, suggesting a conserved role for Wnt signaling in bunyaviral infection. We propose a model where bunyaviruses activate Wnt-responsive genes to regulate optimal cell cycle conditions needed to promote efficient viral replication. The findings in this study should aid in the design of efficacious host-directed antiviral therapeutics. IMPORTANCE RVFV is a mosquito-borne bunyavirus that is endemic to Africa but has demonstrated a capacity for emergence in new territories (e.g., the Arabian Peninsula). As a zoonotic pathogen that primarily affects livestock, RVFV can also cause lethal hemorrhagic fever and encephalitis in humans. Currently, there are no treatments or fully licensed vaccines for this virus. Using high-throughput RNAi screening, we identified canonical Wnt signaling as an important host pathway regulating RVFV infection. The beneficial role of Wnt signaling was observed for RVFV, along with other disparate bunyaviruses, indicating a conserved bunyaviral replication mechanism involving Wnt signaling. Lastly, these studies supplement our knowledge of the fundamental mechanisms of bunyavirus infection and provide new avenues for countermeasure development against pathogenic bunyaviruses.« less

  2. Complete genome sequence and integrated protein localization and interaction map for alfalfa dwarf virus, which combines properties of both cytoplasmic and nuclear plant rhabdoviruses

    SciTech Connect

    Bejerman, Nicolás; Giolitti, Fabián; Breuil, Soledad de; Trucco, Verónica; Nome, Claudia; Lenardon, Sergio; Dietzgen, Ralf G.

    2015-09-15

    Summary: We have determined the full-length 14,491-nucleotide genome sequence of a new plant rhabdovirus, alfalfa dwarf virus (ADV). Seven open reading frames (ORFs) were identified in the antigenomic orientation of the negative-sense, single-stranded viral RNA, in the order 3′-N-P-P3-M-G-P6-L-5′. The ORFs are separated by conserved intergenic regions and the genome coding region is flanked by complementary 3′ leader and 5′ trailer sequences. Phylogenetic analysis of the nucleoprotein amino acid sequence indicated that this alfalfa-infecting rhabdovirus is related to viruses in the genus Cytorhabdovirus. When transiently expressed as GFP fusions in Nicotiana benthamiana leaves, most ADV proteins accumulated in the cell periphery, but unexpectedly P protein was localized exclusively in the nucleus. ADV P protein was shown to have a homotypic, and heterotypic nuclear interactions with N, P3 and M proteins by bimolecular fluorescence complementation. ADV appears unique in that it combines properties of both cytoplasmic and nuclear plant rhabdoviruses. - Highlights: • The complete genome of alfalfa dwarf virus is obtained. • An integrated localization and interaction map for ADV is determined. • ADV has a genome sequence similarity and evolutionary links with cytorhabdoviruses. • ADV protein localization and interaction data show an association with the nucleus. • ADV combines properties of both cytoplasmic and nuclear plant rhabdoviruses.

  3. X-ray structure and inhibition of 3C-like protease from porcine epidemic diarrhea virus

    DOE PAGES [OSTI]

    St. John, Sarah E.; Anson, Brandon J.; Mesecar, Andrew D.

    2016-05-13

    Porcine epidemic diarrhea virus (PEDV) is a coronavirus that infects pigs and can have mortality rates approaching 100% in piglets, causing serious economic impact. The 3C-like protease (3CLpro) is essential for the coronaviral life cycle and is an appealing target for the development of therapeutics. We report the expression, purification, crystallization and 2.10 angstrom X-ray structure of 3CLpro from PEDV. Analysis of the PEDV 3CLpro structure and comparison to other coronaviral 3CLpro's from the same alpha-coronavirus phylogeny shows that the overall structures and active site architectures across 3CLpro's are conserved, with the exception of a loop that comprises the proteasemore » S-2 pocket. We found a known inhibitor of severe acute respiratory syndrome coronavirus (SARS-CoV) 3CLpro, (R)-16, to have inhibitor activity against PEDV 3CLpro, despite that SARS-3CLpro and PEDV 3CLpro share only 45.4% sequence identity. Structural comparison reveals that the majority of residues involved in (R)-16 binding to SARS-3CLpro are conserved in PEDV-3CLpro; however, the sequence variation and positional difference in the loop forming the S-2 pocket may account for large observed difference in IC50 values. In conclusion, this work advances our understanding of the subtle, but important, differences in coronaviral 3CLpro architecture and contributes to the broader structural knowledge of coronaviral 3CLpro's.« less

  4. An intrinsically disordered peptide from Ebola virus VP35 controls viral RNA synthesis by modulating nucleoprotein-RNA interactions

    DOE PAGES [OSTI]

    Leung, Daisy  W.; Borek, Dominika; Luthra, Priya; Binning, Jennifer  M.; Anantpadma, Manu; Liu, Gai; Harvey, Ian B.; Su, Zhaoming; Endlich-Frazier, Ariel; Pan, Juanli; et al

    2015-04-01

    During viral RNA synthesis, Ebola virus (EBOV) nucleoprotein (NP) alternates between an RNA-template-bound form and a template-free form to provide the viral polymerase access to the RNA template. In addition, newly synthesized NP must be prevented from indiscriminately binding to noncognate RNAs. Here, we investigate the molecular bases for these critical processes. We identify an intrinsically disordered peptide derived from EBOV VP35 (NPBP, residues 20–48) that binds NP with high affinity and specificity, inhibits NP oligomerization, and releases RNA from NP-RNA complexes in vitro. The structure of the NPBP/ΔNPNTD complex, solved to 3.7 Å resolution, reveals how NPBP peptide occludesmore » a large surface area that is important for NP-NP and NP-RNA interactions and for viral RNA synthesis. Together, our results identify a highly conserved viral interface that is important for EBOV replication and can be targeted for therapeutic development.« less

  5. Palmitoylation of the feline immunodeficiency virus envelope glycoprotein and its effect on fusion activity and envelope incorporation into virions

    SciTech Connect

    Gonzalez, Silvia A.; Paladino, Monica G.; Affranchino, Jose L.

    2012-06-20

    The feline immunodeficiency virus (FIV) envelope glycoprotein (Env) possesses a short cytoplasmic domain of 53 amino acids containing four highly conserved cysteines at Env positions 804, 811, 815 and 848. Since palmitoylation of transmembrane proteins occurs at or near the membrane anchor, we investigated whether cysteines 804, 811 and 815 are acylated and analyzed the relevance of these residues for Env functions. Replacement of cysteines 804, 811 and 815 individually or in combination by serine residues resulted in Env glycoproteins that were efficiently expressed and processed. However, mutations C804S and C811S reduced Env fusogenicity by 93% and 84%, respectively, compared with wild-type Env. By contrast, mutant C815S exhibited a fusogenic capacity representing 50% of the wild-type value. Remarkably, the double mutation C804S/C811S abrogated both Env fusion activity and Env incorporation into virions. Finally, by means of Click chemistry assays we demonstrated that the four FIV Env cytoplasmic cysteines are palmitoylated.

  6. Iowa State University | OSTI, US Dept of Energy Office of Scientific and

    Office of Scientific and Technical Information (OSTI)

    Technical Information Iowa State University Spotlights Home DOE Applauds Iowa State University Science and Technical Programs Ames Laboratory is a DOE National Laboratory operated under contract by Iowa State University tiny2.jpg Physicist developing, improving designer optical materials tiny3.jpg Chemists discover proton mechanism used by flu virus to infect cells 100.png ISU, Ames Lab's Bryden & McCorkle win 2010 R&D 100 Award NingFangGroup450.jpg New tool for cell research may

  7. The Lettuce infectious yellows virus (LIYV)-encoded P26 is associated with plasmalemma deposits within LIYV-infected cells

    SciTech Connect

    Medina, V.; Sudarshana, M.R.; Tian, T.; Ralston, K.S.; Yeh, H.-H.; Falk, B.W. . E-mail: bwfalk@ucdavis.edu

    2005-03-15

    Cytological, immunological, and mutagenesis approaches were used to identify the viral factors associated with the formation of plasmalemma deposits (PLDs) in whole plants and protoplasts infected by Lettuce infectious yellows virus (LIYV). Transmission electron microscopy and immunogold labeling using polyclonal antibodies to four of the five LIYV RNA 2-encoded large proteins, capsid protein (CP), minor capsid protein (CPm), HSP70 homolog (HSP70h), and P59, showed specific labeling of LIYV virions or virion aggregates around the vesiculated membranous inclusions, but not PLDs in LIYV-infected Nicotiana benthamiana, Nicotiana clevelandii, Lactuca sativa, and Chenopodium murale plants, and Nicotiana tabacum protoplasts. In contrast, antibodies to the RNA 2-encoded P26 showed specific labeling of PLDs but not virions in both LIYV-infected plants and protoplasts. Virion-like particles (VLPs) were seen in protoplasts infected by all LIYV RNA 2 mutants except for the CP (major capsid protein) mutant. PLDs were more difficult to find in protoplasts, but were seen in protoplasts infected by the CP and CPm mutants, but not in protoplasts infected by the P26, HSP70h, or P59 mutants. Interestingly, although the CPm mutant showed VLPs and PLDs, the PLDs did not show associated virions/virion-like particles as was always observed for PLDs seen in protoplasts infected by wild-type LIYV. Immunoblot analyses performed on purified LIYV virions showed that P26 was not detected with purified virions, but was detected in the cell wall, 1000 g and 30,000 g pellet fractions of LIYV-infected plants. These data suggest that P26 is associated with the LIYV-induced PLDs, and in contrast to the other RNA 2-encoded large proteins, P26 is not a virion protein.

  8. Kinetics of interaction of Cotton Leaf Curl Kokhran Virus-Dabawali (CLCuKV-Dab) coat protein and its mutants with ssDNA

    SciTech Connect

    Priyadarshini, C.G. Poornima; Savithri, H.S.

    2009-04-10

    Gemini viral assembly and transport of viral DNA into nucleus for replication, essentially involve DNA-coat protein interactions. The kinetics of interaction of Cotton Leaf Curl Kokhran Virus-Dabawali recombinant coat protein (rCP) with DNA was studied by electrophoretic mobility shift assay (EMSA) and surface plasmon resonance (SPR). The rCP interacted with ssDNA with a K{sub A}, of 2.6 +- 0.29 x 10{sup 8} M{sup -1} in a sequence non-specific manner. The CP has a conserved C2H2 type zinc finger motif composed of residues C68, C72, H81 and H85. Mutation of these residues to alanine resulted in reduced binding to DNA probes. The H85A mutant rCP showed the least binding with approximately 756 fold loss in the association rate and a three order magnitude decrease in the binding affinity as compared to rCP. The CP-DNA interactions via the zinc finger motif could play a crucial role in virus assembly and in nuclear transport.

  9. Role for a region of helically unstable DNA within the Epstein-Barr virus latent cycle origin of DNA replication oriP in origin function

    SciTech Connect

    Polonskaya, Zhanna; Benham, Craig J.; Hearing, Janet . E-mail: jhearing@ms.cc.sunysb.edu

    2004-10-25

    The minimal replicator of the Epstein-Barr virus (EBV) latent cycle origin of DNA replication oriP is composed of two binding sites for the Epstein-Barr virus nuclear antigen-1 (EBNA-1) and flanking inverted repeats that bind the telomere repeat binding factor TRF2. Although not required for minimal replicator activity, additional binding sites for EBNA-1 and TRF2 and one or more auxiliary elements located to the right of the EBNA-1/TRF2 sites are required for the efficient replication of oriP plasmids. Another region of oriP that is predicted to be destabilized by DNA supercoiling is shown here to be an important functional component of oriP. The ability of DNA fragments of unrelated sequence and possessing supercoiled-induced DNA duplex destabilized (SIDD) structures, but not fragments characterized by helically stable DNA, to substitute for this component of oriP demonstrates a role for the SIDD region in the initiation of oriP-plasmid DNA replication.

  10. Overexpression of the human BCL-2 gene product results in growth enhancement of Epstein-Barr virus-immortalized B cells

    SciTech Connect

    Tsujimoto, Yoshihide (Wistar Institute of Anatomy and Biology, Philadelphia, PA (USA))

    1989-03-01

    The biological activity of the human BCL-2 gene product was analyzed in an Epstein-Barr virus (EBV)-infected human lymphoblastoid B-cell line transfected with BCL-2 sequences driven by the simian virus 40 promoter and enhancer. Overproduction of the BCL-2 protein conferred a selective growth advantage to the EBV-infected B cells as compared with control transfectants in low-serum medium and also after seeding at limiting dilution but did not render the cells tumorigenic in athymic nude mice. This growth enhancement was also seen in cells transfected with the BCL-2 gene with its own promoter juxtaposed to the immunoglobulin heavy chain gene enhancer, which represents the translocated form of the BCL-2 gene observed in follicular lymphomas with the t(14;18) translocation. The growth advantage of EBV-infected B cells overproducing the BCL-2 protein is neither due to the enhanced growth factor production nor due to an enhanced sensitivity of the BCL-2 transfectants to interleukins 1 or 6, although both lymphokines are known to stimulate proliferation of EBV-infected B-cell lines. The growth advantage of EBV-infected B-cell lines. The growth advantage of EBV-infected B cells by overproduction of the BCL-2 protein suggests the direct involvement of the BCL-2 gene product in the pathogenesis of follicular lymphoma.

  11. Vaccinia virus temperature-sensitive mutants in the A28 gene produce non-infectious virions that bind to cells but are defective in entry

    SciTech Connect

    Turner, Peter C. Dilling, Bradley P.; Prins, Cindy; Cresawn, Steven G.; Moyer, Richard W.; Condit, Richard C.

    2007-09-15

    The vaccinia virus temperature-sensitive mutations Cts6 and Cts9 were mapped by marker rescue and DNA sequencing to the A28 gene. Cts6 and Cts9 contain an identical 2-bp deletion truncating the A28 protein and removing the fourth conserved cysteine near the C-terminus. Cts9 mutant virions produced at 40 deg. C were non-infectious and unable to cause cytopathic effect. However, the mutant A28 protein localized to purified mature virions (MV) at 31 deg. C and 40 deg. C. MV of Cts9 produced at 40 deg. C bound to cells but did not enter cells. Low pH treatment of Cts9-infected cells at 18 h p.i. failed to produce fusion from within at 40 deg. C, but gave fusion at 31 deg. C. Adsorption of Cts9 mutant virions to cells followed by low pH treatment showed a defect in fusion from without. The Cts9 phenotype suggests that the A28 protein is involved in both virus entry and cell-cell fusion, and supports the linkage between the two processes.

  12. Joint environmental assessment 1997--2001 of the California Department of Food and Agriculture Curly Top Virus Control Program for Bureau of Land Management and Department of Energy

    SciTech Connect

    1997-03-01

    The DOE, Naval Petroleum reserves in California (NPRC), proposes to sign an Amendment to the Cooperative Agreement and Supplement with the California Department of Food and Agriculture (CDFA) to extend the term of the Curly Top Virus Control Program (CTVCP) in California. This program involves Malathion spraying on NPRC lands to control the beet leafhopper, over a five year period from 1997 through 2001. It is expected that approximately 330 acres on Naval Petroleum Reserve Number 1 (NPR-1) and approximately 9,603 acres on Naval Petroleum Reserve Number 2 (NPR-2) will be treated with Malathion annually by CDFA during the course of this program. The actual acreage subject to treatment can vary from year to year. Pursuant to the requirements of the National Environmental Policy Act of 1969 (NEPA), as amended, the potential impacts of the proposed action were analyzed in a Joint Environmental Assessment (DOE/EA-1011) with the US Department of Interior, Bureau of Land Management (BLM) acting as lead agency, in consultation with the CDFA, and the DOE acting as a cooperating agency. Based on the analysis in the EA, DOE has determined that the conduct of the Curly Top Virus Control Program in California is not a major Federal action significantly affecting the quality of the human environment, within the meaning of the NEPA. Therefore, the preparation of an Environmental Impact Statement is not required and DOE is consequently issuing a FONSI.

  13. In vivo subcellular localization of Mal de Rio Cuarto virus (MRCV) non-structural proteins in insect cells reveals their putative functions

    SciTech Connect

    Maroniche, Guillermo A.; Mongelli, Vanesa C.; Llauger, Gabriela; Alfonso, Victoria; Taboga, Oscar

    2012-09-01

    The in vivo subcellular localization of Mal de Rio Cuarto virus (MRCV, Fijivirus, Reoviridae) non-structural proteins fused to GFP was analyzed by confocal microscopy. P5-1 showed a cytoplasmic vesicular-like distribution that was lost upon deleting its PDZ binding TKF motif, suggesting that P5-1 interacts with cellular PDZ proteins. P5-2 located at the nucleus and its nuclear import was affected by the deletion of its basic C-termini. P7-1 and P7-2 also entered the nucleus and therefore, along with P5-2, could function as regulators of host gene expression. P6 located in the cytoplasm and in perinuclear cloud-like inclusions, was driven to P9-1 viroplasm-like structures and co-localized with P7-2, P10 and {alpha}-tubulin, suggesting its involvement in viroplasm formation and viral intracellular movement. Finally, P9-2 was N-glycosylated and located at the plasma membrane in association with filopodia-like protrusions containing actin, suggesting a possible role in virus cell-to-cell movement and spread.

  14. Molecular Foundry

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    NEWS ARCHIVE < News and Highlights Research Performed by Foundry Industrial Users Honored by Nanotechnology Journal User work on printable photonics was selected as a Highlight of the Year by Nanotechnology in the area of "patterning and nano fabrication". [MORE] Outsmarting Thermodynamics in Self-assembly of Nanostructures Foundry user - and Materials Sciences Division Director - reports method for symmetry-breaking in feedback-driven self-assembly of optical metamaterials. [MORE]

  15. Evolution of the human immunodeficiency virus type 2 envelope in the first years of infection is associated with the dynamics of the neutralizing antibody response

    DOE PAGES [OSTI]

    Rocha, Cheila; Calado, Rita; Borrego, Pedro; Marcelino, José Maria; Bártolo, Inês; Rosado, Lino; Cavaco-Silva, Patrícia; Gomes, Perpétua; Família, Carlos; Quintas, Alexandre; et al

    2013-10-24

    Background: therapy and the majority of HIV-2 infected individuals survive as elite controllers with normal CD4+ T cell counts and low or undetectable plasma viral load. Neutralizing antibodies (Nabs) are thought to play a central role in HIV-2 evolution and pathogenesis. However, the dynamic of the Nab response and resulting HIV-2 escape during acute infection and their impact in HIV-2 evolution and disease progression remain largely unknown. Our objective was to characterize the Nab response and the molecular and phenotypic evolution of HIV-2 in association with Nab escape in the first years of infection in two children infected at birth.more » As a result, CD4+ T cells decreased from about 50% to below 30% in both children in the first five years of infection and the infecting R5 viruses were replaced by X4 viruses within the same period. With antiretroviral therapy, viral load in child 1 decreased to undetectable levels and CD4+ T cells recovered to normal levels, which have been sustained at least until the age of 12. In contrast, viral load increased in child 2 and she progressed to AIDS and death at age 9. Beginning in the first year of life, child 1 raised high titers of antibodies that neutralized primary R5 isolates more effectively than X4 isolates, both autologous and heterologous. Child 2 raised a weak X4-specific Nab response that decreased sharply as disease progressed. Rate of evolution, nucleotide and amino acid diversity, and positive selection, were significantly higher in the envelope of child 1 compared to child 2. Rates of R5-to-X4 tropism switch, of V1 and V3 sequence diversification, and of convergence of V3 to a β-hairpin structure were related with rate of escape from the neutralizing antibodies. Finally, our data suggests that the molecular and phenotypic evolution of the human immunodeficiency virus type 2 envelope are related with the dynamics of the neutralizing antibody response providing further support for a model in which Nabs

  16. Non-destructive observation of intact bacteria and viruses in water by the highly sensitive frequency transmission electric-field method based on SEM

    SciTech Connect

    Ogura, Toshihiko

    2014-08-08

    Highlights: We developed a high-sensitive frequency transmission electric-field (FTE) system. The output signal was highly enhanced by applying voltage to a metal layer on SiN. The spatial resolution of new FTE method is 41 nm. New FTE system enables observation of the intact bacteria and virus in water. - Abstract: The high-resolution structural analysis of biological specimens by scanning electron microscopy (SEM) presents several advantages. Until now, wet bacterial specimens have been examined using atmospheric sample holders. However, images of unstained specimens in water using these holders exhibit very poor contrast and heavy radiation damage. Recently, we developed the frequency transmission electric-field (FTE) method, which facilitates the SEM observation of biological specimens in water without radiation damage. However, the signal detection system presents low sensitivity. Therefore, a high EB current is required to generate clear images, and thus reducing spatial resolution and inducing thermal damage to the samples. Here a high-sensitivity detection system is developed for the FTE method, which enhances the output signal amplitude by hundredfold. The detection signal was highly enhanced when voltage was applied to the metal layer on silicon nitride thin film. This enhancement reduced the EB current and improved the spatial resolution as well as the signal-to-noise ratio. The spatial resolution of a high-sensitive FTE system is 41 nm, which is considerably higher than previous FTE system. New FTE system can easily be utilised to examine various unstained biological specimens in water, such as living bacteria and viruses.

  17. Structural insight and flexible features of NS5 proteins from all four serotypes of Dengue virus in solution

    SciTech Connect

    Saw, Wuan Geok; Tria, Giancarlo; Grüber, Ardina; Subramanian Manimekalai, Malathy Sony; Zhao, Yongqian; Chandramohan, Arun; Srinivasan Anand, Ganesh; Matsui, Tsutomu; Weiss, Thomas M.; Vasudevan, Subhash G.; Grüber, Gerhard

    2015-10-31

    Infection by the four serotypes ofDengue virus(DENV-1 to DENV-4) causes an important arthropod-borne viral disease in humans. The multifunctional DENV nonstructural protein 5 (NS5) is essential for capping and replication of the viral RNA and harbours a methyltransferase (MTase) domain and an RNA-dependent RNA polymerase (RdRp) domain. In this study, insights into the overall structure and flexibility of the entire NS5 of all fourDengue virusserotypes in solution are presented for the first time. The solution models derived revealed an arrangement of the full-length NS5 (NS5FL) proteins with the MTase domain positioned at the top of the RdRP domain. The DENV-1 to DENV-4 NS5 forms are elongated and flexible in solution, with DENV-4 NS5 being more compact relative to NS5 from DENV-1, DENV-2 and DENV-3. Solution studies of the individual MTase and RdRp domains show the compactness of the RdRp domain as well as the contribution of the MTase domain and the ten-residue linker region to the flexibility of the entire NS5. Swapping the ten-residue linker between DENV-4 NS5FL and DENV-3 NS5FL demonstrated its importance in MTase–RdRp communication and in concerted interaction with viral and host proteins, as probed by amide hydrogen/deuterium mass spectrometry. Conformational alterations owing to RNA binding are presented.

  18. Hepatitis B virus X protein mutant HBxΔ127 promotes proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT

    SciTech Connect

    Liu, Fabao; You, Xiaona; Chi, Xiumei; Wang, Tao; Ye, Lihong; Niu, Junqi; Zhang, Xiaodong

    2014-02-07

    Highlights: • Relative to wild type HBx, HBX mutant HBxΔ127 strongly enhances cell proliferation. • Relative to wild type HBx, HBxΔ127 remarkably up-regulates miR-215 in hepatoma cells. • HBxΔ127-elevated miR-215 promotes cell proliferation via targeting PTPRT mRNA. - Abstract: The mutant of virus is a frequent event. Hepatitis B virus X protein (HBx) plays a vital role in the development of hepatocellular carcinoma (HCC). Therefore, the identification of potent mutant of HBx in hepatocarcinogenesis is significant. Previously, we identified a natural mutant of the HBx gene (termed HBxΔ127). Relative to wild type HBx, HBxΔ127 strongly enhanced cell proliferation and migration in HCC. In this study, we aim to explore the mechanism of HBxΔ127 in promotion of proliferation of hepatoma cells. Our data showed that both wild type HBx and HBxΔ127 could increase the expression of miR-215 in hepatoma HepG2 and H7402 cells. However, HBxΔ127 was able to significantly increase miR-215 expression relative to wild type HBx in the cells. We identified that protein tyrosine phosphatase, receptor type T (PTPRT) was one of the target genes of miR-215 through targeting 3′UTR of PTPRT mRNA. In function, miR-215 was able to promote the proliferation of hepatoma cells. Meanwhile anti-miR-215 could partially abolish the enhancement of cell proliferation mediated by HBxΔ127 in vitro. Knockdown of PTPRT by siRNA could distinctly suppress the decrease of cell proliferation mediated by anti-miR-215 in HepG2-XΔ127/H7402-XΔ127 cells. Moreover, we found that anti-miR-215 remarkably inhibited the tumor growth of hepatoma cells in nude mice. Collectively, relative to wild type HBx, HBxΔ127 strongly enhances proliferation of hepatoma cells through up-regulating miR-215 targeting PTPRT. Our finding provides new insights into the mechanism of HBx mutant HBxΔ127 in promotion of proliferation of hepatoma cells.

  19. Heme oxygenase-1 induction alters chemokine regulation and ameliorates human immunodeficiency virus-type-1 infection in lipopolysaccharide-stimulated macrophages

    SciTech Connect

    Zhou, Zhao-Hua; Kumari, Namita; Nekhai, Sergei; Clouse, Kathleen A.; Wahl, Larry M.; Yamada, Kenneth M.; Dhawan, Subhash

    2013-06-07

    Highlights: Lipopolysaccharide stimulation of heme oxygenase-1 (HO-1) ameliorated HIV-1 infection of primary human macrophages. The partial protection by HO-1 against HIV infection was associated with induction of chemokines such as MIP1? and MIP1?. This mechanism explains lipopolysaccharide-stimulated HO-1-mediated inhibition of HIV-1 infection of macrophages. -- Abstract: We have elucidated a putative mechanism for the host resistance against HIV-1 infection of primary human monocyte-derived macrophages (MDM) stimulated with lipopolysaccharide (LPS). We show that LPS-activated MDM both inhibited HIV-1 entry into the cells and were refractory to post-entry productive viral replication. LPS-treated cells were virtually negative for mature virions as revealed by transmission electron microscopy. LPS activation of MDM markedly enhanced the expression of heme oxygenase-1 (HO-1), a potent inducible cytoprotective enzyme. Increased HO-1 expression was accompanied by elevated production of macrophage inflammatory chemokines (MIP1? and MIP1?) by LPS-activated MDM, significantly decreased surface chemokine receptor-5 (CCR-5) expression, and substantially reduced virus replication. Treatment of cells with HO-1 inhibitor SnPP IX (tin protoporphyrin IX) attenuated the LPS-mediated responses, HIV-1 replication and secretion of MIP1?, MIP1?, and LD78? chemokines with little change in surface CCR-5 expression. These results identify a novel role for HO-1 in the modulation of host immune response against HIV infection of MDM.

  20. The tale of a modern animal plague: Tracing the evolutionary history and determining the time-scale for foot and mouth disease virus

    SciTech Connect

    Tully, Damien C. Fares, Mario A.

    2008-12-20

    Despite significant advances made in the understanding of its epidemiology, foot and mouth disease virus (FMDV) is among the most unexpected agricultural devastating plagues. While the disease manifests itself as seven immunologically distinct strains their origin, population dynamics, migration patterns and divergence times remain unknown. Herein we have assembled a comprehensive data set of gene sequences representing the global diversity of the disease and inferred the time-scale and evolutionary history for FMDV. Serotype-specific rates of evolution and divergence times were estimated using a Bayesian coalescent framework. We report that an ancient precursor FMDV gave rise to two major diversification events spanning a relatively short interval of time. This radiation event is estimated to have taken place towards the end of the 17th and the beginning of the 18th century giving us the present circulating Euro-Asiatic and South African viral strains. Furthermore our results hint that Europe acted as a possible hub for the disease from where it successfully dispersed elsewhere via exploration and trading routes.

  1. Mutational analysis of three predicted 5'-proximal stem-loop structures in the genome of tick-borne encephalitis virus indicates different roles in RNA replication and translation

    SciTech Connect

    Rouha, Harald; Hoenninger, Verena M.; Thurner, Caroline; Mandl, Christian W.

    2011-08-15

    Flavivirus gene expression is modulated by RNA secondary structure elements at the terminal ends of the viral RNA molecule. For tick-borne encephalitis virus (TBEV), four stem-loop (SL) elements have been predicted in the first 180 nucleotides of the viral genome: 5'-SL1, 5'-SL2, 5'-SL3 and 5'-SL4. The last three of these appear to be unique to tick-borne flaviviruses. Here, we report their characterization by mutagenesis in a TBEV luciferase reporter system. By manipulating their thermodynamic properties, we found that an optimal stability of the 5'-SL2 is required for efficient RNA replication. 5'-SL3 formation is also important for viral RNA replication, but although it contains the viral start codon, its formation is dispensable for RNA translation. 5'-SL4 appears to facilitate both RNA translation and replication. Our data suggest that maintenance of the balanced thermodynamic stability of these SL elements is important for temporal regulation of its different functions.

  2. Structural Analysis of a Viral Ovarian Tumor Domain Protease from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded Ubiquitin

    SciTech Connect

    Capodagli, Glenn C.; McKercher, Marissa A.; Baker, Erica A.; Masters, Emily M.; Brunzelle, Joseph S.; Pegan, Scott D.

    2014-10-02

    Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, single-stranded RNA [ssRNA(-)] nairovirus that produces fever, prostration, and severe hemorrhages in humans. With fatality rates for CCHF ranging up to 70% based on several factors, CCHF is considered a dangerous emerging disease. Originally identified in the former Soviet Union and the Congo, CCHF has rapidly spread across large sections of Europe, Asia, and Africa. Recent reports have identified a viral homologue of the ovarian tumor protease superfamily (vOTU) within its L protein. This protease has subsequently been implicated in downregulation of the type I interferon immune response through cleavage of posttranslational modifying proteins ubiquitin (Ub) and the Ub-like interferon-simulated gene 15 (ISG15). Additionally, homologues of vOTU have been suggested to perform similar roles in the positive-sense, single-stranded RNA [ssRNA(+)] arteriviruses. By utilizing X-ray crystallographic techniques, the structure of vOTU covalently bound to ubiquitin propylamine, a suicide substrate of the enzyme, was elucidated to 1.7 {angstrom}, revealing unique structural elements that define this new subclass of the OTU superfamily. In addition, kinetic studies were carried out with aminomethylcoumarin (AMC) conjugates of monomeric Ub, ISG15, and NEDD8 (neural precursor cell expressed, developmentally downregulated 8) substrates in order to provide quantitative insights into vOTU's preference for Ub and Ub-like substrates.

  3. Flow cytometric detection of human immunodeficiency virus type 1 proviral DNA by the polymerase chain reaction incorporating digoxigenin- or fluorescein-labeled dUTP

    SciTech Connect

    Yang, Gang; Olson, J.C.; Pu, R.; Vyas, G.N.

    1995-10-01

    Serological assays are routinely used in the laboratory diagnosis of human immunodeficiency virus type-1 (HrV-1) infection, but the polymerase chain reaction (PCR) is ultimately the most sensitive and direct method for establishing definitive diagnosis. As an alternative to the conventional radioactive PCR procedure we have developed and evaluated a pair of rapid nonradioisotopic flow cytometric detection methods. Using heminested PCR we directly incorporated fluorescein-12-dUTP (fluo-dUTP) or digoxigenin-11-dUTP (dig-dUTP) into the PCR-amplicons. The labeled amplicons were hybridized with biotinylated antisense and sense probes, followed by capture of the hybrid DNA using streptavidin-coated beads which were finally analyzed in a flow cytometer by (1) direct detection of the fluorescence intensity of the amplicons incorporating fluo-dUTP and (2) immunodetection of the amplicons incorporating dig-dUTP by anti-digoxigenin IgG labeled with fluorescein isothiocyanate (FITC). Although both assays were functionally comparable with radiolabeled probe in reliably detecting as low as five copies of HIV-1 proviral DNA sequences, the immunodetection of dig-dUTP consistently yielded higher mean channel fluorescence and gave a stable signal over an extended period of 12-14 weeks. In testing a panel of 20 pedigreed PBMC specimens from blood donors with or without HIV-1 infection, the results of both flow cytometric assays were identical with those of the conventional radioactive procedure. Therefore, we conclude that the dig-dUTP incorporation in amplicons, hybridization with a pair of sense-antisense biotinylated probes and immunodetection of hybrids by flow cytometric analyses is the nonisotopic method of choice for PCR-diagnosis of HIV-1 infection. 21 refs., 2 figs., 4 tabs.

  4. Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk Domain Reveals a Four-Helix Bundle and the Role of the Stalk in Fusion Promotion

    SciTech Connect

    Bose, Sayantan; Welch, Brett D.; Kors, Christopher A.; Yuan, Ping; Jardetzky, Theodore S.; Lamb, Robert A.

    2014-10-02

    Paramyxovirus entry into cells requires the fusion protein (F) and a receptor binding protein (hemagglutinin-neuraminidase [HN], H, or G). The multifunctional HN protein of some paramyxoviruses, besides functioning as the receptor (sialic acid) binding protein (hemagglutinin activity) and the receptor-destroying protein (neuraminidase activity), enhances F activity, presumably by lowering the activation energy required for F to mediate fusion of viral and cellular membranes. Before or upon receptor binding by the HN globular head, F is believed to interact with the HN stalk. Unfortunately, until recently none of the receptor binding protein crystal structures have shown electron density for the stalk domain. Parainfluenza virus 5 (PIV5) HN exists as a noncovalent dimer-of-dimers on the surface of cells, linked by a single disulfide bond in the stalk. Here we present the crystal structure of the PIV5-HN stalk domain at a resolution of 2.65 {angstrom}, revealing a four-helix bundle (4HB) with an upper (N-terminal) straight region and a lower (C-terminal) supercoiled part. The hydrophobic core residues are a mix of an 11-mer repeat and a 3- to 4-heptad repeat. To functionally characterize the role of the HN stalk in F interactions and fusion, we designed mutants along the PIV5-HN stalk that are N-glycosylated to physically disrupt F-HN interactions. By extensive study of receptor binding, neuraminidase activity, oligomerization, and fusion-promoting functions of the mutant proteins, we found a correlation between the position of the N-glycosylation mutants on the stalk structure and their neuraminidase activities as well as their abilities to promote fusion.

  5. Metronomic Adjuvant Chemotherapy Improves Treatment Outcome in Nasopharyngeal Carcinoma Patients With Postradiation Persistently Detectable Plasma Epstein-Barr Virus Deoxyribonucleic Acid

    SciTech Connect

    Twu, Chih-Wen; Wang, Wen-Yi; Chen, Chien-Chih; Liang, Kai-Li; Jiang, Rong-San; Wu, Ching-Te; Shih, Yi-Ting; Lin, Po-Ju; Liu, Yi-Chun; Lin, Jin-Ching

    2014-05-01

    Purpose: To investigate the effects of adjuvant chemotherapy in nasopharyngeal carcinoma (NPC) patients with persistently detectable plasma Epstein-Barr virus DNA (pEBV DNA) after curative radiation therapy plus induction/concurrent chemotherapy. Methods and Materials: The study population consisted of 625 NPC patients with available pEBV DNA levels before and after treatment. Eighty-five patients with persistently detectable pEBV DNA after 1 week of completing radiation therapy were eligible for this retrospective study. Of the 85 patients, 33 were administered adjuvant chemotherapy consisting of oral tegafur-uracil (2 capsules twice daily) for 12 months with (n=4) or without (n=29) preceding intravenous chemotherapy of mitomycin-C, epirubicin, and cisplatin. The remaining 52 patients who did not receive adjuvant chemotherapy served as the control group. Results: Baseline patient characteristics at diagnosis (age, sex, pathologic type, performance status, T classification, N classification, and overall stage), as well as previous treatment modality, were comparable in both arms. After a median follow-up of 70 months for surviving patients, 45.5% (15 of 33 patients) with adjuvant chemotherapy and 71.2% (37 of 52 patients) without adjuvant chemotherapy experienced tumor relapses (P=.0323). There were a significant reduction in distant failure (P=.0034) but not in local or regional recurrence. The 5-year overall survival rate was 71.6% for patients with adjuvant chemotherapy and 28.7% for patients without adjuvant chemotherapy (hazard ratio 0.27; 95% confidence interval 0.17-0.55; P<.0001). Conclusions: Our retrospective data showed that adjuvant chemotherapy can reduce distant failure and improve overall survival in NPC patients with persistently detectable pEBV DNA after curative radiation therapy plus induction/concurrent chemotherapy.

  6. Glycoprotein 5 of porcine reproductive and respiratory syndrome virus strain SD16 inhibits viral replication and causes G2/M cell cycle arrest, but does not induce cellular apoptosis in Marc-145 cells

    SciTech Connect

    Mu, Yang; Li, Liangliang; Zhang, Beibei; Huang, Baicheng; Gao, Jiming; and others

    2015-10-15

    Cell apoptosis is common after infection with porcine reproductive and respiratory syndrome virus (PRRSV). PRRSV GP5 has been reported to induce cell apoptosis. To further understand the role of GP5 in PRRSV induced cell apoptosis, we established Marc-145 cell lines stably expressing full-length GP5, GP5{sup Δ84-96} (aa 84-96 deletion), and GP5{sup Δ97-119} (aa 97-119 deletion). Cell proliferation, cell cycle progression, cell apoptosis and virus replication in these cell lines were evaluated. Neither truncated nor full-length GP5 induced cell apoptosis in Marc-145 cells. However, GP5{sup Δ97-119}, but not full-length or GP5{sup Δ84-96}, induced a cell cycle arrest at the G2/M phase resulting in a reduction in the growth of Marc-145 cells. Additionally, GP5{sup Δ84-96} inhibited the replication of PRRSV in Marc-145 cells through induction of IFN-β. These findings suggest that PRRSV GP5 is not responsible for inducing cell apoptosis in Marc-145 cells under these experimental conditions; however it has other important roles in virus/host cell biology. - Highlights: • Marc-145 cell lines stable expression PRRSV GP5 or truncated GP5 were constructed. • GP5{sup Δ97-119} expression in Marc-145 cell induced cell cycle arrest at G2/M phase. • Expression of GP5 and truncated GP5 could not induce Marc-145 cells apoptosis. • PRRSV replication in Marc-145-GP5{sup Δ84-96} was significantly inhibited.

  7. Conserved amino acids of the human immunodeficiency virus type 2 Vpx nuclear localization signal are critical for nuclear targeting of the viral preintegration complex in non-dividing cells

    SciTech Connect

    Belshan, Michael; Mahnke, Lisa A.; Ratner, Lee . E-mail: lratner@im.wustl.edu

    2006-03-01

    The HIV-2 viral accessory protein Vpx is related to, but distinct from the Vpr protein of HIV-1. Vpx is packaged into virions and as a component of the viral preintegration complex (PIC) is required for efficient virus replication in non-dividing cells. We have previously reported that the minimal transferable region of Vpx that contained karyophilic properties was aa 65 to 72. Analysis of Vpx sequences from various HIV-2/SIV strains reveals that this region contains highly conserved amino acids, including two basic residues (K68, R70) and three tyrosines (Y66, Y69, Y71). Here, we demonstrate that mutation of the basic or tyrosine residues abolishes PIC nuclear import in arrested cells as assessed by PCR detection of viral integration. Examination of cell-free virus by Western blot indicated that all mutant proteins were incorporated into virions, suggesting that the lack of replication in arrested cells was not due to a loss of Vpx in target cells. Together, these studies map critical residues of the Vpx nuclear localization signal that are required for efficient infection of non-dividing cells.

  8. Microbiome associations in pigs with the best and worst clinical outcomes following co-infection with porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2)

    DOE PAGES [OSTI]

    Niederwerder, Megan C.; Jaing, Crystal J.; Thissen, James B.; Cino-Ozuna, Ada Giselle; McLoughlin, Kevin S.; Rowland, Raymond R. R.

    2016-03-10

    Co-infections involving porcine reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) are common and contribute to a range of polymicrobial disease syndromes in swine and on a world-wide basis. Both viruses compromise host defenses, resulting in increased susceptibility to infections by primary and secondary pathogens that can affect growth performance as well as increased morbidity and mortality. An experimental population of 95 pigs was co-infected with PRRSV and PCV2. At 70 days post-infection (dpi), 20 representative pigs were selected as having the best or worst clinical outcome based on average daily gain (ADG) and the presencemore » of clinical disease. Moreover, the worst clinical outcome pigs had prolonged and greater levels of viremia as measured by qPCR. Serum, lung and fecal samples collected at 70 dpi were analyzed using a comprehensive DNA microarray technology, the Lawrence Livermore Microbial Detection Array, to detect over 8000 microbes. Bacterial species, such as Bacillus cereus, were detected at a higher rate in the serum of worst performing pigs. At the level of the fecal microbiome, the overall microbial diversity was lower in the worst clinical outcome group. The results reinforce the importance of pathogen load in determining clinical outcome and suggest an important role of microbial diversity as a contributing factor in disease.« less

  9. High-Sensitivity C-Reactive Protein Complements Plasma Epstein-Barr Virus Deoxyribonucleic Acid Prognostication in Nasopharyngeal Carcinoma: A Large-Scale Retrospective and Prospective Cohort Study

    SciTech Connect

    Tang, Lin-Quan; Li, Chao-Feng; Chen, Qiu-Yan; Zhang, Lu; Lai, Xiao-Ping; He, Yun; Xu, Yun-Xiu-Xiu; Hu, Dong-Peng; Wen, Shi-Hua; Peng, Yu-Tuan; Chen, Wen-Hui; Liu, Huai; Guo, Shan-Shan; Liu, Li-Ting; Li, Jing; Zhang, Jing-Ping; and others

    2015-02-01

    Purpose: To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of nasopharyngeal carcinoma (NPC). Patients and Methods: Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis–free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared. Results: Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis–free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging. Conclusion: Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.

  10. Zika Virus Disease and Prevention

    Energy.gov [DOE] (indexed site)

    Most common symptoms of Zika are fever, rash, joint pain, or conjunctivitis (red eyes). ... they develop a fever, rash, joint pain, or red eyes during their trip or within 2 weeks ...

  11. Feeling the burn: Understanding how biomass burning changes climate

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Feeling the burn: Understanding how biomass burning changes climate Feeling the burn: Understanding how biomass burning changes climate When black carbon from fires is released into the atmosphere, it can mean bad news for the climate. At least half of the black carbon in the atmosphere is a result of biomass burning. September 27, 2016 x x PDF 2016 Curiosity rover finds weird 'egg rock' meteorite on Mars Outsmarting the art of camouflage Smoking a pack a day for a year leaves 150 mutations in

  12. 2010 | U.S. DOE Office of Science (SC)

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    0 News News Home Featured Articles 2016 2015 2014 2013 2012 2011 2010 2009 2008 2007 2006 2005 Science Headlines Science Highlights Presentations & Testimony News Archives Communications and Public Affairs Contact Information Office of Science U.S. Department of Energy 1000 Independence Ave., SW Washington, DC 20585 P: (202) 586-5430 Featured Articles 2010 Print Text Size: A A A FeedbackShare Page A line of windmills in the sunset 12.27.10From the Labs Outsmarting the Wind External link

  13. Downregulation of miRNA-30c and miR-203a is associated with hepatitis C virus core protein-induced epithelial–mesenchymal transition in normal hepatocytes and hepatocellular carcinoma cells

    SciTech Connect

    Liu, Dongjing; Wu, Jilin; Liu, Meizhou; Yin, Hui; He, Jiantai; Zhang, Bo

    2015-09-04

    Hepatitis C virus (HCV) Core protein has been demonstrated to induce epithelial–mesenchymal transition (EMT) and is associated with cancer progression of hepatocellular carcinoma (HCC). However, how the Core protein regulates EMT is still unclear. In this study, HCV Core protein was overexpressed by an adenovirus. The protein levels of EMT markers were measured by Western blot. The xenograft animal model was established by inoculation of HepG2 cells. Results showed that ectopic expression of HCV core protein induced EMT in L02 hepatocytes and HepG2 tumor cells by upregulating vimentin, Sanl1, and Snal2 expression and downregulating E-cadherin expression. Moreover, Core protein downregulated miR-30c and miR-203a levels in L02 and HepG2 cells, but artificial expression of miR-30c and miR-203a reversed Core protein-induced EMT. Further analysis showed that ectopic expression of HCV core protein stimulated cell proliferation, inhibited apoptosis, and increased cell migration, whereas artificial expression of miR-30c and miR-203a significantly reversed the role of Core protein in these cell functions in L02 and HepG2 cells. In the HepG2 xenograft tumor models, artificial expression of miR-30c and miR-203a inhibited EMT and tumor growth. Moreover, L02 cells overexpressing Core protein can form tumors in nude mice. In HCC patients, HCV infection significantly shortened patients' survival time, and loss of miR-30c and miR-203 expression correlated with poor survival. In conclusion, HCV core protein downregulates miR-30c and miR-203a expression, which results in activation of EMT in normal hepatocytes and HCC tumor cells. The Core protein-activated-EMT is involved in the carcinogenesis and progression of HCC. Loss of miR-30c and miR-203a expression is a marker for the poor prognosis of HCC. - Highlights: • HCV core protein downregulates miR-30c and miR-203a expression. • Downregulation of miR-30c and miR-203a activates EMT. • Activated-EMT is involved in the

  14. Residues R{sup 199}H{sup 200} of prototype foamy virus transactivator Bel1 contribute to its binding with LTR and IP promoters but not its nuclear localization

    SciTech Connect

    Ma, Qinglin; Tan, Juan; Cui, Xiaoxu; Luo, Di; Yu, Miao; Liang, Chen; Qiao, Wentao

    2014-01-20

    Prototype foamy virus encodes a transactivator called Bel1 that enhances viral gene transcription and is essential for PFV replication. Nuclear localization of Bel1 has been reported to rely on two proximal basic motifs R{sup 199}H{sup 200} and R{sup 221}R{sup 222}R{sup 223} that likely function together as a bipartite nuclear localization signal. In this study, we report that mutating R{sup 221}R{sup 222}R{sup 223}, but not R{sup 199}H{sup 200}, relocates Bel1 from the nucleus to the cytoplasm, suggesting an essential role for R{sup 221}R{sup 222}R{sup 223} in the nuclear localization of Bel1. Although not affecting the nuclear localization of Bel1, mutating R{sup 199}H{sup 200} disables Bel1 from transactivating PFV promoters. Results of EMSA reveal that the R{sup 199}H{sup 200} residues are vital for the binding of Bel1 to viral promoter DNA. Moreover, mutating R{sup 199}H{sup 200} in Bel1 impairs PFV replication to a much greater extent than mutating R{sup 221}R{sup 222}R{sup 223}. Collectively, our findings suggest that R{sup 199}H{sup 200} directly participate in Bel1 binding to viral promoter DNA and are indispensible for Bel1 transactivation activity. - Highlights: • The R{sup 221}R{sup 222}R{sup 223} residues are essential for the nuclear localization of Bel1. • Although not affecting the nuclear localization of Bel1, mutating R{sup 199}H{sup 200} disables Bel1 from transactivating PFV promoters. • The R{sup 199}H{sup 200} residues directly participate in Bel1 binding to viral promoter DNA. • Mutating R{sup 199}H{sup 200} in Bel1 impairs PFV replication to a much greater extent than mutating R{sup 221}R{sup 222}R{sup 223}.

  15. One Vaccine Leads to Another

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    particular-have led to vaccines against other diseases, like the flu and bacterial meningitis. Often, nontoxic forms of various disease toxins are used to make vaccines,...

  16. Activated Carbon Injection

    ScienceCinema

    None

    2014-07-22

    History of the Clean Air Act and how the injection of carbon into a coal power plant's flu smoke can reduce the amount of mercury in the smoke.

  17. Activated Carbon Injection

    SciTech Connect

    2014-07-16

    History of the Clean Air Act and how the injection of carbon into a coal power plant's flu smoke can reduce the amount of mercury in the smoke.

  18. 1

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    can say this because of the model they have constructed. Using historical data, a mathematical representation of how flu spreads through a population, and data for the current...

  19. ALSNews Vol. 338

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    to the future of scientific research. Read more... Toward Design of a Universal Flu Vaccine Scientists have determined the structures of antibodies that protect against broad...

  20. ORISE: Process and Program Evaluation

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    (measles, mumps and rubella) vaccine Immunization of health care workers against 2009 influenza A (H1N1) Vaccination of CDC employees against seasonal flu Factors influencing...

  1. 1663 March 2013

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Spotlights Safer nuclear power Alternative fuel rod cladding materials make a Fukushima-type explosion much less likely Preventing a pandemic Simulations of a flu pandemic ...

  2. Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

    SciTech Connect

    Smith, Clyde

    2005-04-26

    According to Smith, protein crystallography allows scientists to design drugs in a much more efficient way than the standard methods traditionally used by large drug companies, which can cost close to a billion dollars and take 10 to 15 years. 'A lot of the work can be compressed down,' Smith said. Protein crystallography enables researchers to learn the structure of molecules involved in disease and health. Seeing the loops, folds and placement of atoms in anything from a virus to a healthy cell membrane gives important information about how these things work - and how to encourage, sidestep or stop their functions. Drug design can be much faster when the relationship between structure and function tells you what area of a molecule to target. Smith will use a timeline to illustrate the traditional methods of drug development and the new ways it can be done now. 'It is very exciting work. There have been some failures, but many successes too.' A new drug to combat the flu was developed in a year or so. Smith will tell us how. He will also highlight drugs developed to combat HIV, Tuberculosis, hypertension and Anthrax.

  3. Site Index - HPMC Occupational Health Services

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Flu Prevention Hand Washing Healthy Sleep Heat Stress Radon Signs of a Heart Attack "Cough CPR:" Urban Myth Signs of a Stroke Coping with Stress & Change Skin Cancer Awareness...

  4. Science Summary

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    H1N1 Flu Links Scientific Highlight Wilson Lab Scripps Press Release Scripps ... A group of researchers led by Prof. Ian Wilson of The Scripps Research Institute has found ...

  5. ORISE: H1N1 Media Analysis | How ORISE is Making a Difference

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    H1N1 map This map represents the geographic origin or location of daily news articles related to H1N1 flu. The map is generated out of ORISE's Auto-INFORM database, which...

  6. 1

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    the Los Alamos scientist who leads the project. "Holiday travel and the rate at which people get flu shots can change the forecast, so we'll continue to update the model as ...

  7. Inspection Report: IG-0784 | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) (indexed site)

    December 19, 2007 The Department of Energy's Pandemic Influenza Planning According to the ... of its workforce, could become sick from a mutated avian influenza (bird flu) H5N1 strain. ...

  8. Community Connections: November 2016

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    November 2016 Community Connections: Your link to news and opportunities from Los Alamos National Laboratory Latest Issue:November 2, 2016 all issues All Issues » submit IN THIS ISSUE Laboratory helps veterans seeking employment Training summits discuss how to recruit, hire, and retain vets Make Thanksgiving brighter for a local family Donate today to the Laboratory's annual food drive Forecasting the flu in New Mexico Data helps scientists predict the peak and severity of flu season Lab

  9. Human immunodeficiency virus type 1 clade M mosaic gag polypeptides

    DOEpatents

    Korber, Bette T; Perkins, Simon; Bhattacharya, Tanmoy; Fischer, William M; Theiler, James; Letvin, Norman; Haynes, Barton F; Hahn, Beatrice H; Yusim, Karina; Kuiken, Carla

    2015-04-21

    The present invention relates to mosaic HIV-1 group M Gag sequences and to a composition comprising same.

  10. Genomics-enabled sensor platform for rapid detection of viruses...

    Office of Scientific and Technical Information (OSTI)

    Currently, diagnosis of acute infections requires amplification of viral nucleic acids, which can be costly, highly specific, technically challenging and time consuming. No ...

  11. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    analysis. A small number of the top proteins were expressed and purified from E. coli, and further binding tests selected two proteins that bound to BHRF1 with acceptable...

  12. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    up the question of whether there are other transformers or morpheeins that exist in biology and may even be linked to human disease. Research conducted by: Z.A. Bornholdt,...

  13. Genomics-enabled sensor platform for rapid detection of viruses...

    Office of Scientific and Technical Information (OSTI)

    recognized through reportable diseases by health departments and reports of unusual ... (arboviruses) have emerged as some of the most significant threats to human health. ...

  14. Virus-based Piezoelectric Energy Generation - Energy Innovation...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    that it is possible to modulate the dipole strength of the phage, hence tuning the piezoelectric response, by genetically engineering the major coat proteins of the phage. ...

  15. Mosaic protein and nucleic acid vaccines against hepatitis C virus

    DOEpatents

    Yusim, Karina; Korber, Bette T. M.; Kuiken, Carla L.; Fischer, William M.

    2013-06-11

    The invention relates to immunogenic compositions useful as HCV vaccines. Provided are HCV mosaic polypeptide and nucleic acid compositions which provide higher levels of T-cell epitope coverage while minimizing the occurrence of unnatural and rare epitopes compared to natural HCV polypeptides and consensus HCV sequences.

  16. Designer Proteins Target Epstein-Barr-Virus-Associated Cancer

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    The crystal structure of Epstein-Barr Viral BHRF1 (black) bound to a designed protein ... The study shows not just how to help defeat EBV, but also opens up a whole new way to ...

  17. Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins

    DOEpatents

    Korber, Bette T.; Perkins, Simon; Bhattacharya, Tanmoy; Fischer, William M.; Theiler, James; Letvin, Norman; Haynes, Barton F.; Hahn, Beatrice H.; Yusim, Karina; Kuiken, Carla

    2012-02-21

    The present invention relates to mosaic clade M HIV-1 Nef polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  18. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Society for the Promotion of Science, and the Japan Ministry of Education, Culture, Sports, Science, and Technology. Operation of the ALS is supported by the U.S. Department of...

  19. Structure of the Ebola Virus Glycoprotein Bound to an Antibody...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Bound to an Antibody from a Human Survivor Print Ebolavirus, one of two members of the family of filoviruses, causes a severe hemorrhagic fever with 50-90% human mortality. ...

  20. Discovering multi-scale co-occurrence patterns of asthma and influenza with the Oak Ridge bio-surveillance toolkit

    SciTech Connect

    Ramanathan, Arvind; Pullum, Laura L.; Hobson, Tanner C.; Stahl, Christopher G.; Steed, Chad A.; Valkova, Silvia; Quinn, Shannon; Chennubhotla, Chakra

    2015-08-03

    Here, we describe a data-driven unsupervised machine learning approach to extract geo-temporal co-occurrence patterns of asthma and the flu from large-scale electronic healthcare reimbursement claims (eHRC) datasets. Specifically, we examine the eHRC data from 2009 to 2010 pandemic H1N1 influenza season and analyze whether different geographic regions within the United States (US) showed an increase in co-occurrence patterns of the flu and asthma. Our analyses reveal that the temporal patterns extracted from the eHRC data show a distinct lag time between the peak incidence of the asthma and the flu. While the increased occurrence of asthma contributed to increased flu incidence during the pandemic, this co-occurrence is predominant for female patients. The geo-temporal patterns reveal that the co-occurrence of the flu and asthma are typically concentrated within the south-east US. Further, in agreement with previous studies, large urban areas (such as New York, Miami, and Los Angeles) exhibit co-occurrence patterns that suggest a peak incidence of asthma and flu significantly early in the spring and winter seasons. Together, our data-analytic approach, integrated within the Oak Ridge Bio-surveillance Toolkit platform, demonstrates how eHRC data can provide novel insights into co-occurring disease patterns.

  1. Multiplex Degenerate Primer Design for Targeted Whole Genome...

    Office of Scientific and Technical Information (OSTI)

    fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus. ...

  2. A new spin: Adapting SpinDx for Use in Low-Resource Environment

    Office of Scientific and Technical Information (OSTI)

    ... Pneumo-enteritis Syndrome Infectious bovine rhinotracheitis virus Sheep and goat pox viruses Bluetongue virus Bluetongue virus Oral erosions syndromic panel (>

  3. Discovering multi-scale co-occurrence patterns of asthma and influenza with the Oak Ridge bio-surveillance toolkit

    DOE PAGES [OSTI]

    Ramanathan, Arvind; Pullum, Laura L.; Hobson, Tanner C.; Stahl, Christopher G.; Steed, Chad A.; Valkova, Silvia; Quinn, Shannon; Chennubhotla, Chakra

    2015-08-03

    Here, we describe a data-driven unsupervised machine learning approach to extract geo-temporal co-occurrence patterns of asthma and the flu from large-scale electronic healthcare reimbursement claims (eHRC) datasets. Specifically, we examine the eHRC data from 2009 to 2010 pandemic H1N1 influenza season and analyze whether different geographic regions within the United States (US) showed an increase in co-occurrence patterns of the flu and asthma. Our analyses reveal that the temporal patterns extracted from the eHRC data show a distinct lag time between the peak incidence of the asthma and the flu. While the increased occurrence of asthma contributed to increased flumore » incidence during the pandemic, this co-occurrence is predominant for female patients. The geo-temporal patterns reveal that the co-occurrence of the flu and asthma are typically concentrated within the south-east US. Further, in agreement with previous studies, large urban areas (such as New York, Miami, and Los Angeles) exhibit co-occurrence patterns that suggest a peak incidence of asthma and flu significantly early in the spring and winter seasons. Together, our data-analytic approach, integrated within the Oak Ridge Bio-surveillance Toolkit platform, demonstrates how eHRC data can provide novel insights into co-occurring disease patterns.« less

  4. Happenings @ AL Month | The Ames Laboratory

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    October 2016 « Prev Next » Event Type - Any - Audit/Review Holiday Lab Wide Retirement Speaker/Demo Training Visitors Apply Sun Mon Tue Wed Thu Fri Sat 25 26 27 28 29 30 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 Flu Shot Clinic » Fair Labor Standards Act Information Update 140 TASF 1:00am 16 17 18 19 20 21 22 « Flu Shot Clinic Being Prepared for the Unexpected. Safety in your office and public places. 301A Spedding 10:00am 23 24 25 26 27 28 29 Hot Work and Open Flame Safety (AL-149) 140 TASF

  5. Text and Structural Data Mining of Influenza Mentions in Web and Social Media

    SciTech Connect

    Corley, Courtney D.; Cook, Diane; Mikler, Armin R.; Singh, Karan P.

    2010-02-22

    Text and structural data mining of Web and social media (WSM) provides a novel disease surveillance resource and can identify online communities for targeted public health communications (PHC) to assure wide dissemination of pertinent information. WSM that mention influenza are harvested over a 24-week period, 5-October-2008 to 21-March-2009. Link analysis reveals communities for targeted PHC. Text mining is shown to identify trends in flu posts that correlate to real-world influenza-like-illness patient report data. We also bring to bear a graph-based data mining technique to detect anomalies among flu blogs connected by publisher type, links, and user-tags.

  6. Nucleic acids encoding modified human immunodeficiency virus type 1 (HIV-1) group M consensus envelope glycoproteins

    DOEpatents

    Haynes, Barton F.; Gao, Feng; Korber, Bette T.; Hahn, Beatrice H.; Shaw, George M.; Kothe, Denise; Li, Ying Ying; Decker, Julie; Liao, Hua-Xin

    2011-12-06

    The present invention relates, in general, to an immunogen and, in particular, to an immunogen for inducing antibodies that neutralizes a wide spectrum of HIV primary isolates and/or to an immunogen that induces a T cell immune response. The invention also relates to a method of inducing anti-HIV antibodies, and/or to a method of inducing a T cell immune response, using such an immunogen. The invention further relates to nucleic acid sequences encoding the present immunogens.

  7. Mosaic clade M human immunodeficiency virus type 1 (HIV-1) envelope immunogens

    DOEpatents

    Korber, Bette T.; Fischer, William; Liao, Hua-Xin; Haynes, Barton F.; Letvin, Norman; Hahn; Beatrice H.

    2011-05-31

    The present invention relates to mosaic clade M HIV-1 Env polypeptides and to compositions comprising same. The polypeptides of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  8. Nucleic acids encoding mosaic clade M human immunodeficiency virus type 1 (HIV-1) envelope immunogens

    DOEpatents

    Korber, Bette T; Fischer, William; Liao, Hua-Xin; Haynes, Barton F; Letvin, Norman; Hahn, Beatrice H

    2015-04-21

    The present invention relates to nucleic acids encoding mosaic clade M HIV-1 Env polypeptides and to compositions and vectors comprising same. The nucleic acids of the invention are suitable for use in inducing an immune response to HIV-1 in a human.

  9. Viruses in laboratory-reared cactus moth, Cactoblastis cactorum (Lepidoptera: Pyralidae)

    SciTech Connect

    Marti, O.G.; Myers, R.E.; Carpenter, J.E.; Styer, E.L.

    2007-03-15

    The cactus moth, Cactoblastis cactorum (Lepidoptera: Pyralidae: Phycitinae), is a non-native species threatening a variety of native cacti, particularly endangered species of Opuntia (Zimmerman et al. 2001), on the coast of the Gulf of Mexico. Cactoblastis cactorum populations have expanded from Florida northward along the Atlantic coast as far as Charleston, SC, and westward along the Gulf of Mexico to Dauphin Island, south of Mobile, AL. It is feared that further movement to the west will allow C. cactorum to enter the US desert Southwest and Mexico, particularly the latter. Numerous cactus species, especially those of the genera Opuntia and Nopalea, are native to the U.S. and Mexico. Local economies based on agricultural and horticultural uses of cacti could be devastated by C. cactorum (Vigueras and Portillo 2001). A bi-national control program between the US and Mexico is being developed, utilizing the sterile insect technique (SIT). In the SIT program, newly emerged moths are irradiated with a {sup 60}Co source and released to mate with wild individuals. The radiation dose completely sterilizes the females and partially sterilizes the males. When irradiated males mate with wild females, the F1 progeny of these matings are sterile. In order for the SIT program to succeed, large numbers of moths must be reared from egg to adult on artificial diet in a quarantined rearing facility (Carpenter et al. 2001). Irradiated insects must then be released in large numbers at the leading edge of the invasive population and at times which coincide with the presence of wild individuals available for mating. Mortality from disease in the rearing colony disrupts the SIT program by reducing the numbers of insects available for release.

  10. Multipronged attenuation of macrophage-colony stimulating factor signaling by Epstein-Barr virus BARF1

    SciTech Connect

    Shim, Ann Hye-Ryong; Chang, Rhoda Ahn; Chen, Xiaoyan; Longnecker, Richard; He, Xiaolin

    2014-10-02

    The ubiquitous EBV causes infectious mononucleosis and is associated with several types of cancers. The EBV genome encodes an early gene product, BARF1, which contributes to pathogenesis, potentially through growth-altering and immune-modulating activities, but the mechanisms for such activities are poorly understood. We have determined the crystal structure of BARF1 in complex with human macrophage-colony stimulating factor (M-CSF), a hematopoietic cytokine with pleiotropic functions in development and immune response. BARF1 and M-CSF form a high-affinity, stable, ring-like complex in both solution and the crystal, with a BARF1 hexameric ring surrounded by three M-CSF dimers in triangular array. The binding of BARF1 to M-CSF dramatically reduces but does not completely abolish M-CSF binding and signaling through its cognate receptor FMS. A three-pronged down-regulation mechanism is proposed to explain the biological effect of BARF1 on M-CSF:FMS signaling. These prongs entail control of the circulating and effective local M-CSF concentration, perturbation of the receptor-binding surface of M-CSF, and imposition of an unfavorable global orientation of the M-CSF dimer. Each prong may reduce M-CSF:FMS signaling to a limited extent but in combination may alter M-CSF:FMS signaling dramatically. The downregulating mechanism of BARF1 underlines a viral modulation strategy, and provides a basis for understanding EBV pathogenesis.

  11. Analysis of phases in the structure determination of an icosahedral virus

    SciTech Connect

    Plevka, Pavel; Kaufmann, Bärbel; Rossmann, Michael G.

    2012-03-15

    The constraints imposed on structure-factor phases by noncrystallographic symmetry (NCS) allow phase improvement, phase extension to higher resolution and hence ab initio phase determination. The more numerous the NCS redundancy and the greater the volume used for solvent flattening, the greater the power for phase determination. In a case analyzed here the icosahedral NCS phasing appeared to have broken down, although later successful phase extension was possible when the envelope around the NCS region was tightened. The phases from the failed phase-determination attempt fell into four classes, all of which satisfied the NCS constraints. These four classes corresponded to the correct solution, opposite enantiomorph, Babinet inversion and opposite enantiomorph with Babinet inversion. These incorrect solutions can be seeded from structure factors belonging to reciprocal-space volumes that lie close to icosahedral NCS axes where the structure amplitudes tend to be large and the phases tend to be 0 or {pi}. Furthermore, the false solutions can spread more easily if there are large errors in defining the envelope designating the region in which NCS averaging is performed.

  12. Discovery of Disease Co-occurrence Patterns from Electronic Healthcare Reimbursement Claims Data

    SciTech Connect

    Ramanathan, Arvind; Pullum, Laura L; Hobson, Tanner C; Quinn, Shannon; Chennubhotla, Chakra; Valkova, Silvia

    2014-01-01

    Effective public health surveillance is important for national secu- rity. With novel emerging infectious diseases being reported across different parts of the world, there is a need to build effective bio- surveillance systems that can track, monitor and report such events in a timely manner. Additionally, there is a need to identify sus- ceptible geographic regions/populations where these diseases may have a significant impact and design preemptive strategies to tackle them. With the digitization of health related information through electronic health records (EHR) and electronic healthcare claim re- imbursements (eHCR), there is a tremendous opportunity to ex- ploit these datasets for public health surveillance. In this paper, we present our analysis on the use of eHCR data for bio-surveillance by studying the 2009-2010 H1N1 pandemic flu season. We present a novel approach to extract spatial and temporal patterns of flu in- cidence across the United States (US) from eHCRs and find that a small, but distinct set of break-out patterns govern the flu and asthma incidence rates across the entire country. Further, we ob- serve a distinct temporal lag in the onset of flu when compared to asthma across geographic regions in the US. The patterns extracted from the data collectively indicate how these break-out patterns are coupled, even though the flu represents an infectious disease whereas asthma represents a typical chronic condition. Taken to- gether, our approach demonstrates how mining eHCRs can provide novel insights in tackling public health concerns.

  13. Time-Resolved Small-Angle X-ray Scattering Studies Revealed Three...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Stages of a T4 Virus Maturation Most eukaryotic viruses, including HIV, influenza and herpes viruses, undergo maturation when transitioning from the noninfectious provirion to the...

  14. SSRL HEADLINES April 2009

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    0 April, 2009 __________________________________________________________________________ Contents of this Issue: User Safety Update Caution Advised Regarding Swine Flu Outbreak Science Highlight - Novel Mechanism for DNA Biosynthesis in Organisms with Gene thyX could Lead to Better Antibiotics Science Highlight - Finding the Crystal Structure of P-gp: A Protein that Makes Cancer Cells Resistant to Chemotherapy Science Highlight - A New Way to Limit Damaging Production of Nitric Oxide From the

  15. SSRL HEADLINES May 2010

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    1 May, 2010 __________________________________________________________________________ Contents of this Issue: Science Highlight - Archaeopteryx Feathers and Bone Chemistry Fully Revealed via Synchrotron Imaging Science Highlight - Structural Basis for Senior Immunity to the Current H1N1 Flu Science Highlight - Suspected Copper Chelator Binds not just Copper but Copper-Protein Trimer Complexes From the Acting Director of SSRL: Where Do We Go from Here? SPEAR3 Increased Current and Frequent Fill

  16. News Item

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    4, 2014 Time: 11:00 am Speaker: Dr. David Baker, University of Washington Title: Design of Protein Structures, Functions and Assemblies Location: 67-3111 Chemla Room Hosted by Ron Zuckermann Abstract: I will describe recent advances in computational protein design which allow the generation of new protein structures and functions. I will describe the use of these methods to design ultra-stable idealized proteins, flu neutralizing proteins, high affinity ligand binding proteins, and self

  17. Structure of a bacterial virus DNA-injection protein complex reveals a decameric assembly with a constricted molecular channel

    DOE PAGES [OSTI]

    Zhao, Haiyan; Speir, Jeffrey A.; Matsui, Tsutomu; Lin, Zihan; Liang, Lingfei; Lynn, Anna Y.; Varnado, Brittany; Weiss, Thomas M.; Tang, Liang; Schuch, Raymond

    2016-02-16

    The multi-layered cell envelope structure of Gram-negative bacteria represents significant physical and chemical barriers for short-tailed phages to inject phage DNA into the host cytoplasm. Here we show that a DNA-injection protein of bacteriophage Sf6, gp12, forms a 465-kDa, decameric assembly in vitro. The electron microscopic structure of the gp12 assembly shows a ~150-Å, mushroom-like architecture consisting of a crown domain and a tube-like domain, which embraces a 25-Å-wide channel that could precisely accommodate dsDNA. The constricted channel suggests that gp12 mediates rapid, uni-directional injection of phage DNA into host cells by providing a molecular conduit for DNA translocation. Themore » assembly exhibits a 10-fold symmetry, which may be a common feature among DNA-injection proteins of P22-like phages and may suggest a symmetry mismatch with respect to the 6-fold symmetric phage tail. As a result, the gp12 monomer is highly flexible in solution, supporting a mechanism for translocation of the protein through the conduit of the phage tail toward the host cell envelope, where it assembles into a DNA-injection device.« less

  18. The effects of 5-fluorouracil and doxorubicin on expression of human immunodeficiency virus type 1 long terminal repeat

    SciTech Connect

    Panozzo, J.; Akan, E.; Griffiths, T.D.; Woloschak, G.E.

    1996-03-01

    Previous work by many groups has documented induction of the HIV-LTR following exposure of cells to ultraviolet light and other DNA damaging agents. Our experiments set out to determine the relative activation or repression of the HIV-LTR in response to two classes of chemotherapeutic agents: Doxorubicin is a DNA-damage inducing agent, and 5-fluorouracil has an antimetabolic mode of action. Using HeLa cells stably transfected with a construct in which HIV-LTR drives expression of the chloramphenicol acetyl transferase reporter gene, we demonstrated an up to 10-fold induction following doxorubicin treatment in 24 h post-treatment. This induction was repressed by treatment with salicylic acid, suggesting a role for prostaglandin/cyclo-oxygenase pathways and/or NFKB in the inductive response. Induction by 5-fluorouracil, in contrast, was more modest (two-fold at most) though it was consistently elevated over controls.

  19. Science Summary

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    conformational changes and auto-proteolysis. Like many human viruses such as HIV and herpes virus, NwV, an insect virus, requires these specific structural changes to become...

  20. Biochemical and Structural Insights into the Preference of Nairoviral...

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    The enzymatic activities of vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from humans, ...

  1. In the OSTI Collections: Neutron Sources for Studying Matter...

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    ... When a virus infects the cells of its host, the cells' functioning is taken over by the virus so that the cells replicate numerous copies of the virus, which may then be released ...

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    ... The enzymatic activities ofmore vOTUs originating from the Crimean-Congo hemorrhagic fever virus, Erve virus, and Nairobi sheep disease virus were tested against ISG15s from ...

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    ... that inhibits the replication of many viruses such as Moloney murine leukemia virus (MLV) and Sindbis virus (SIN) by preventing the accumulation of viral mRNA in the cytoplasm. ...

  4. Recombination elevates the effective evolutionary rate and facilitates...

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    replication competent virus is detected even when other forms may have been transmitted. ... Subject: 59 BASIC BIOLOGICAL SCIENCES HV-1; MTCT; transmittedfounder virus; ...

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    ... of latent genomic fragments in the plasma virus population Immonen, Taina T. ; Conway, ... Virus released from activated latent cells competes against variants that have continually ...

  6. "Title","Creator/Author","Publication Date","OSTI Identifier...

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    ... Virus andor bacteria are pathogens that can be transported by the disclosed method. ... Virus andor bacteria are pathogens that can be transported by the disclosed method. ...

  7. Rational design and adaptive management of combination therapies...

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    therapies for Hepatitis C virus infection Prev Next Title: Rational design and adaptive management of combination therapies for Hepatitis C virus infection Recent ...

  8. Rational Design and Adaptive Management of Combination Therapies...

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    of Combination Therapies for Hepatitis C Virus Infection CrossMark click for updates n ... Design and Adaptive Management of Combination Therapies for Hepatitis C Virus Infection. ...

  9. Search for: microbes OR Microbiomes | DOE PAGES

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    ... reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ... reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ...

  10. Microbiome associations in pigs with the best and worst clinical...

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    reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ... reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ...

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    ... Structure of the Newcastle disease virus hemagglutinin-neuraminidase (HN) ectodomain ... Mutations of the Newcastle disease virus HN stalk region have been shown to affect both F ...

  12. AFV CoverSheet

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    of Latent Genomic Fragments in the Plasma Virus Population Immonen, Taina Tuulia Conway, ... of Latent Genomic Fragments in the Plasma Virus Population Taina T. Immonen 1 *, Jessica ...

  13. Recombination enhances HIV-1 envelope diversity by facilitating...

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    plasma virus population Prev Next Title: Recombination enhances HIV-1 envelope diversity by facilitating the survival of latent genomic fragments in the plasma virus ...

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    ... in the Setting of Human Immunodeficiency Virus Klein, Emily A. ; Guiou, Michael ; ... head-and-neck cancer among a cohort of patients with human immunodeficiency virus (HIV). ...

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    Structure of a Bacterial Virus DNA-Injection Protein Complex Reveals a Decameric Assembly ... Liang April 2014 Structures of minute virus of mice replication initiator protein ...

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    ... Assembly of the Ebola Virus Nucleoprotein from a Chaperoned VP35 Complex Kirchdoerfer, ... Hepatitis B Virus Capsids Have Diverse Structural Responses to Small-Molecule Ligands ...

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    ... Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to ... porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. ...

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    ... Filter Results Filter by Subject aids virus (1) basic biological sciences (1) design (1) ... Hepatitis C Virus E2 Envelope Glycoprotein Core Structure Kong, Leopold ; Giang, Erick ; ...

  19. Structure of the cleavage-activated prefusion form of the parainfluenz...

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    the parainfluenza virus 5 fusion protein Citation Details In-Document Search Title: Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein ...

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    ... replication competent virus is detected even when other forms may have been transmitted. ... of latent genomic fragments in the plasma virus population Immonen, Taina T. ; Conway, ...

  1. Strategic Priming with Multiple Antigens can Yield Memory Cell...

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    ... Protective vaccines against smallpox (Vaccinia virus) produce T cell populations that are ... CD8+ T cell immunodominance in primary and secondary influenza virus infections. J. Exp. ...

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    of latent genomic fragments in the plasma virus population Immonen, Taina T. ; Conway, ... Virus released from activated latent cells competes against variants that have continually ...

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    ... of the cauliflower mosaic virus 35S promoter, a commonly used promoter in plant biology. ... of mannopine synthase promoter and cauliflower mosaic virus 35S promoter enhancer region). ...

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    ... Severe Acute Respiratory Syndrome corona virus (SARS-CoV) represent a serious public ... genesproteins likely related to the pathogenicity of SARS-CoV and influenza virus. ...

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    ... Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein ... We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation ...

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    ... (2) glycoproteins (2) affinity (1) aids virus (1) antibodies (1) antigens (1) ... Antibody Recognition of the Pandemic H1N1 Influenza Virus Hemagglutinin Receptor Binding ...

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    Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for ... Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for ...

  8. Hydrodynamic and Membrane Binding Properties of Purified Rous...

    Office of Scientific and Technical Information (OSTI)

    Purified Rous Sarcoma Virus Gag Protein Citation Details In-Document Search Title: Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein ...

  9. Microsoft Word - Ch 1-Ch9-umai-thesis.doc

    Office of Scientific and Technical Information (OSTI)

    ... as the tobacco mosaic virus, collagen, capsid 116, tubulin117, or actin118, 119. ... and dimensionalities were obtained with DNA 180-183, virus 184 and peptides 179. ...

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    ... and development of computational tools to predict virus-host protein interactions. ... goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. ...

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    ... Conformational changes in Sindbis virus induced by decreased pH revealed by small-angle ... William T Alphaviruses, such as Sindbis virus, undergo dramatic changes in ...

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    Solution Properties of Murine Leukemia Virus Gag Protein: Differences from HIV-1 Gag ... We now describe the properties of the Gag protein of Moloney murine leukemia virus ...

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    Hydrodynamic and Membrane Binding Properties of Purified Rous Sarcoma Virus Gag Protein ... We have purified Rous sarcoma virus (RSV) Gag protein and in parallel several truncation ...

  14. DOE Grant DEFG02-95ER25253 Final Report Development of Simulation...

    Office of Scientific and Technical Information (OSTI)

    Development of Simulation Tools for Virus Shell Assembly Bonnie Berger Introduction Prof. ... Significant progress has been made in the following areas relating to virus shell ...

  15. Program

    Office of Scientific and Technical Information (OSTI)

    ... (RNAPs) from virus, bacteriophage, bacteria and eukaryote, but not from archaebacteria. ... of the genus Acidianus. The rod-shaped virus ARV1 was assigned to the family ...

  16. After the Nobel Prize, What Do You Do for an Encore? | U.S. DOE...

    Office of Science (SC)

    illustrates how the ABEL Trap can corral individual particles of tobacco mosaic virus. ... illustrates how the ABEL Trap can corral individual particles of tobacco mosaic virus. ...

  17. User Facilities: Tools for Seeing Atoms | U.S. DOE Office of...

    Office of Science (SC)

    ... Enlarge Photo X-ray diffraction of a single virus particle. Scattering or diffraction ... X-ray diffraction of virus: T. Ekeberg, Uppsala University. Orbitals in metal oxide: ...

  18. Vignettes | U.S. DOE Office of Science (SC)

    Office of Science (SC)

    ... hypericin, which upon exposure to light is toxic to tumors and HIV, the human AIDS virus. ... Pathogens thus far detected with good sensitivity include an influenza virus, cholera ...

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    ... Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for ... Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for ...

  20. In the OSTI Collections: Genomics | OSTI, US Dept of Energy Office...

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    ... The investigators "generated and characterized suitable primers for West Nile Virus RNA ... Phenotype Arthropod Arthropod-borne virus (Arbovirus) Allele combinatorial Structural ...

  1. Search for: microbes OR Microbiomes | DOE PAGES

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    reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ... reproductive and respiratory syndrome virus (PRRSV) and porcine circovirus type 2 ...

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    ... renormalization (3) trajectories (3) aids virus (2) basic biological sciences (2) lattice ... Full Text Available December 2014 Human immunodeficiency virus type 1 clade M mosaic gag ...

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    ... Valley Fever Virus infection Harmon, Brooke ; Bird, Sara W. ; Schudel, Benjamin R. ; Hatch, Anson V. ; Rasley, Amy ; Negrete, Oscar A. Rift Valley fever virus (RVFV) is an ...

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    ... Filter Results Filter by Subject applied life sciences (9) aids virus (6) glycoproteins ... rearrangements to mediate virus entry into cells and to evade the host immune response. ...

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    ... are host cell targets for the matrix (M) protein of vesicular stomatitis virus (VSV). ... by the vesicular stomatitis virus matrix protein to inhibit host cell nuclear export. ...

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    ... Anal Carcinoma in Human Immunodeficiency Virus-Positive Patients Receiving Highly Active ... anal carcinoma in human immunodeficiency virus (HIV)-infected patients receiving highly ...

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    renormalization (3) trajectories (3) aids virus (2) basic biological sciences (2) lattice ... Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins ...

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    nanotemplates of Tobacco mosaic virus using atomic layer deposition, exhibiting ... the patterning and templated synthesis of virus-structured nanomaterials in two- and ...

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    ... January 2008 A Novel Approach to Unknown Virus Identification in Clinical Samples. La ... February 2014 A Novel Approach to Unknown Virus Detection in Clinical Samples. La Bauve, ...

  10. Mathematical and Statistical Opportunities in Cyber Security

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    ... and virus detection based on an immunological distinction between "self and "nonself." Using the analogy between an immune system they have studied problems in computer virus ...

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    ... from the Crimean-Congo Hemorrhagic Fever Virus in Complex with Covalently Bonded ... Crimean-Congo hemorrhagic fever (CCHF) virus is a tick-borne, negative-sense, ...

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    ... (2) spinal cord (2) accuracy (1) aids virus (1) animal tissues (1) applied life ... immunodeficiency virus-positive (HIV+) and 3 post-solid organ transplant ID patients. ...

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    ... NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir Furukawa, Ayako ; Okamura, Hideyasu ; Morishita, Ryo ; Department of Microbiology, ...

  14. Search for: shape memory* | DOE PAGES

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    ... of latent genomic fragments in the plasma virus population Immonen, Taina T. ; Conway, ... Virus released from activated latent cells competes against variants that have continually ...

  15. Solid flexible electrochemical supercapacitor using Tobacco mosaic...

    Office of Scientific and Technical Information (OSTI)

    mosaic virus nanostructures and ALD ruthenium oxide Citation Details In-Document Search Title: Solid flexible electrochemical supercapacitor using Tobacco mosaic virus ...

  16. Analysis of the Argonne distance tabletop exercise method.

    SciTech Connect

    Tanzman, E. A.; Nieves, L. A.; Decision and Information Sciences

    2008-02-14

    The purpose of this report is to summarize and evaluate the Argonne Distance Tabletop Exercise (DISTEX) method. DISTEX is intended to facilitate multi-organization, multi-objective tabletop emergency response exercises that permit players to participate from their own facility's incident command center. This report is based on experience during its first use during the FluNami 2007 exercise, which took place from September 19-October 17, 2007. FluNami 2007 exercised the response of local public health officials and hospitals to a hypothetical pandemic flu outbreak. The underlying purpose of the DISTEX method is to make tabletop exercising more effective and more convenient for playing organizations. It combines elements of traditional tabletop exercising, such as scenario discussions and scenario injects, with distance learning technologies. This distance-learning approach also allows playing organizations to include a broader range of staff in the exercise. An average of 81.25 persons participated in each weekly webcast session from all playing organizations combined. The DISTEX method required development of several components. The exercise objectives were based on the U.S. Department of Homeland Security's Target Capabilities List. The ten playing organizations included four public health departments and six hospitals in the Chicago area. An extent-of-play agreement identified the objectives applicable to each organization. A scenario was developed to drive the exercise over its five-week life. Weekly problem-solving task sets were designed to address objectives that could not be addressed fully during webcast sessions, as well as to involve additional playing organization staff. Injects were developed to drive play between webcast sessions, and, in some cases, featured mock media stories based in part on player actions as identified from the problem-solving tasks. The weekly 90-minute webcast sessions were discussions among the playing organizations that were

  17. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    SciTech Connect

    Theunissen, P.T.; Robinson, J.F.; Department of Toxicogenomics, Maastricht University, Maastricht; Netherlands Toxicogenomics Centre, Maastricht ; Pennings, J.L.A.; Netherlands Toxicogenomics Centre, Maastricht ; Herwijnen, M.H. van; Kleinjans, J.C.S.; Netherlands Toxicogenomics Centre, Maastricht ; Piersma, A.H.; Netherlands Toxicogenomics Centre, Maastricht; Institute for Risk Assessment Sciences, Faculty of Veterinary Sciences, Utrecht University, Utrecht

    2012-08-01

    Alternative assays for developmental toxicity testing are needed to reduce animal use in regulatory toxicology. The in vitro murine neural embryonic stem cell test (ESTn) was designed as an alternative for neurodevelopmental toxicity testing. The integration of toxicogenomic-based approaches may further increase predictivity as well as provide insight into underlying mechanisms of developmental toxicity. In the present study, we investigated concentration-dependent effects of six mechanistically diverse compounds, acetaldehyde (ACE), carbamazepine (CBZ), flusilazole (FLU), monoethylhexyl phthalate (MEHP), penicillin G (PENG) and phenytoin (PHE), on the transcriptome and neural differentiation in the ESTn. All compounds with the exception of PENG altered ESTn morphology (cytotoxicity and neural differentiation) in a concentration-dependent manner. Compound induced gene expression changes and corresponding enriched gene ontology biological processes (GO–BP) were identified after 24 h exposure at equipotent differentiation-inhibiting concentrations of the compounds. Both compound-specific and common gene expression changes were observed between subsets of tested compounds, in terms of significance, magnitude of regulation and functionality. For example, ACE, CBZ and FLU induced robust changes in number of significantly altered genes (≥ 687 genes) as well as a variety of GO–BP, as compared to MEHP, PHE and PENG (≤ 55 genes with no significant changes in GO–BP observed). Genes associated with developmentally related processes (embryonic morphogenesis, neuron differentiation, and Wnt signaling) showed diverse regulation after exposure to ACE, CBZ and FLU. In addition, gene expression and GO–BP enrichment showed concentration dependence, allowing discrimination of non-toxic versus toxic concentrations on the basis of transcriptomics. This information may be used to define adaptive versus toxic responses at the transcriptome level.

  18. Hybrid fluidized bed combuster

    DOEpatents

    Kantesaria, Prabhudas P.; Matthews, Francis T.

    1982-01-01

    A first atmospheric bubbling fluidized bed furnace is combined with a second turbulent, circulating fluidized bed furnace to produce heat efficiently from crushed solid fuel. The bed of the second furnace receives the smaller sizes of crushed solid fuel, unreacted limestone from the first bed, and elutriated solids extracted from the flu gases of the first bed. The two-stage combustion of crushed solid fuel provides a system with an efficiency greater than available with use of a single furnace of a fluidized bed.

  19. May Events

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    May May 2016 Events May 2016 event highlights May 9 Mon 8:00 AM Energy Landscapes: From Protein Folding to Molecular Assembly Hilton Santa Fe Historic Plaza - Santa Fe, NM Nanoscale molecular assembly is very common in biology and in nanotechnology. May 14 Sat 11:00 AM From biofuels to predicting the flu Bradbury Science Museum - 1350 Central Ave, Los Alamos, NM 87544, USA Scientist in the Spotlight: A chance to chat with scientists about their work May 16 Mon 8:00 AM Data Science and Optimal

  20. 2014 - 09 | Jefferson Lab

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    9 Sep 2014 Tue, 2014-09-30 16:53 Performance Appraisal Process Begins Today, 9/29/2014 Mon, 2014-09-29 15:02 Occupational Medicine Offers Staff Flu Vaccines by Appointment Thu, 2014-09-25 08:45 12 GeV CEBAF Upgrade Celebration to Be Held on Friday Wed, 2014-09-24 17:39 Hall D and Accelerator Service Buildings Radiological Status Change Tue, 2014-09-23 09:35 Got 18 Minutes? Catch a TEDx talk on Wednesday, Sept. 24 Mon, 2014-09-22 17:19 Jefferson Lab Fitness Center Open House Set for Oct. 6, 11:30

  1. Science on Tap - Forecasting illness

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Science on Tap - Forecasting illness Science on Tap - Forecasting illness WHEN: Mar 17, 2016 5:30 PM - 7:00 PM WHERE: UnQuarked Wine Room 145 Central Park Square, Los Alamos, New Mexico 87544 USA CONTACT: Linda Anderman (505) 665-9196 CATEGORY: Bradbury INTERNAL: Calendar Login Event Description Mark your calendars for this event held every third Thursday from 5:30 to 7 p.m. A short presentation is followed by a lively discussion on a different subject each month. Forecasting the flu (and other

  2. BSM Newsletter February 2016

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    February 2016 At the Bradbury Latest Issue:November 2016 all issues All Issues » submit IN THIS ISSUE What do you think of our new look and feel? A short survey on our new look February most likely month for flu season to peak From our pages Inspecting a microscope A new artifact joins our collection Tobacco and radiation? Our science question of the month Top 10 science stories of the year From our pages Conifer disappearance due to climate change? From our pages EVENTS What's the matter with

  3. ORBiT: Oak Ridge Bio-surveillance Toolkit for Public Health Dynamics

    SciTech Connect

    Ramanathan, Arvind; Pullum, Laura L; Hobson, Tanner C; Steed, Chad A; Chennubhotla, Chakra; Quinn, Shannon

    2015-01-01

    With novel emerging infectious diseases being reported across different parts of the world, there is a need to build effective bio-surveillance systems that can track, monitor and report such events in a timely manner. Apart from monitoring for emerging disease outbreaks, it is also important to identify susceptible geographic regions and populations where these diseases may have a significant impact. The digitization of health related information through electronic health records (EHR) and electronic healthcare claim reimbursements (eHCR) and the continued growth of self-reported health information through social media provides both tremendous opportunities and challenges in developing novel public health surveillance tools. In this paper, we present an overview of Oak Ridge Bio-surveillance Toolkit (ORBiT), which we have developed specifically to address data analytic challenges in the realm of public health surveillance. In particular, ORBiT provides an extensible environment to pull together diverse, large-scale datasets and analyze them to identify spatial and temporal patterns for various bio-surveillance related tasks. We demonstrate the utility of ORBiT in automatically extracting a small number of spatial and temporal patterns during the 2009-2010 pandemic H1N1 flu season using eHCR data. These patterns provide quantitative insights into the dynamics of how the pandemic flu spread across different parts of the country. We discovered that the eHCR data exhibits multi-scale patterns from which we could identify a small number of states in the United States (US) that act as bridge regions contributing to one or more specific influenza spread patterns. Similar to previous studies, the patterns show that the south-eastern regions of the US were widely affected by the H1N1 flu pandemic. Several of these south-eastern states act as bridge regions, which connect the north-east and central US in terms of flu occurrences. These quantitative insights show how the e

  4. Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles

    SciTech Connect

    Pinto, Ligia A.; Harro, Clayton D.; Kemp, Troy J.; Lowy, Douglas R.; Schiller, John T.; Berzofsky, Jay A.; Hildesheim, Allan

    2006-09-30

    Human papillomavirus-like particles (HPV VLP) are candidate vaccines that have shown to be efficacious in reducing infection and inducing robust antiviral immunity. Neutralizing antibodies generated by vaccination are largely type-specific, but little is known about the type-specificity of cellular immune responses to VLP vaccination. To determine whether vaccination with HPV-16 L1VLP induces cellular immunity to heterologous HPV types (HPV-18, HPV-31, and HPV-53), we examined proliferative and cytokine responses in vaccine (n = 11) and placebo (n = 5) recipients. Increased proliferative and cytokine responses to heterologous types were observed postvaccination in some individuals. The proportion of women responding to heterologous types postvaccination (36%-55%) was lower than that observed in response to HPV-16 (73%). Response to HPV-16 VLP predicted response to other types. The strongest correlations in response were observed between HPV-16 and HPV-31, consistent with their phylogenetic relatedness. In summary, PBMC from HPV-16 VLP vaccine recipients can respond to L1VLP from heterologous HPV types, suggesting the presence of conserved T cell epitopes.

  5. A role for granulocyte-macrophage colony-stimulating factor in the regulation of CD8{sup +} T cell responses to rabies virus

    SciTech Connect

    Wanjalla, Celestine N.; Goldstein, Elizabeth F.; Wirblich, Christoph; Schnell, Matthias J.

    2012-05-10

    Inflammatory cytokines have a significant role in altering the innate and adaptive arms of immune responses. Here, we analyzed the effect of GM-CSF on a RABV-vaccine vector co-expressing HIV-1 Gag. To this end, we immunized mice with RABV expressing HIV-1 Gag and GM-CSF and analyzed the primary and recall CD8{sup +} T cell responses. We observed a statistically significant increase in antigen presenting cells (APCs) in the spleen and draining lymph nodes in response to GM-CSF. Despite the increase in APCs, the primary and memory anti HIV-1 CD8{sup +} T cell response was significantly lower. This was partly likely due to lower levels of proliferation in the spleen. Animals treated with GM-CSF neutralizing antibodies restored the CD8{sup +} T cell response. These data define a role of GM-CSF expression, in the regulation of the CD8{sup +} T cell immune responses against RABV and has implications in the use of GM-CSF as a molecular adjuvant in vaccine development.

  6. Quantitative autoradiography of muscarinic and benzodiazepine receptors in the forebrain of the turtle, Pseudemys scripta

    SciTech Connect

    Schlegel, J.R.; Kriegstein, A.R.

    1987-11-22

    The distribution of muscarinic and benzodiazepine receptors was investigated in the turtle forebrain by the technique of in vitro receptor autoradiography. Muscarinic binding sites were labeled with 1 nM /sup 3/H-quinuclidinyl benzilate (/sup 3/H-QNB), and benzodiazepine sites were demonstrated with the aid of 1 nM /sup 3/H-flunitrazepam (/sup 3/H-FLU). Autoradiograms generated on /sup 3/H-Ultrofilm apposed to tissue slices revealed regionally specific distributions of muscarinic and benzodiazepine binding sites that are comparable with those for mammalian brain. Dense benzodiazepine binding was found in the anterior olfactory nucleus, the lateral and dorsal cortices, and the dorsal ventricular ridge (DVR), a structure with no clear mammalian homologue. Muscarinic binding sites were most dense in the striatum, accumbens, DVR, lateral geniculate, and the anterior olfactory nucleus. Cortical binding sites were studied in greater detail by quantitative analysis of autoradiograms generated by using emulsion-coated coverslips. Laminar gradients of binding were observed that were specific for each radioligand; /sup 3/H-QNB sites were most dense in the inner molecular layer in all cortical regions, whereas /sup 3/H-FLU binding was generally most concentrated in the outer molecular layer and was least dense through all layers in the dorsomedial cortex. Because pyramidal cells are arranged in register in turtle cortex, the laminar patterns of receptor binding may reflect different receptor density gradients along pyramidal cell dendrites.

  7. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... The inhibition of PI3K-Akt activation by LY294002 significantly reduced the viral yield, including a reduction in budded viruses and occlusion bodies. The virus production was ...

  8. Patents -- Ivar Giaever (1976)

    Office of Scientific and Technical Information (OSTI)

    ... used to provide large and widely-distributed surface area for sorting out and separating select viruses, bacteria and other cells from multi-cell, bacteria or virus populations. ...

  9. ALSNews Vol. 354

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    4 Print ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus, termedVP40, undergoes dramatic...

  10. ALSNews Vol. 354

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    ALSNews Vol. 354 Print ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus, termedVP40, undergoes...

  11. ALSNews Vol. 354

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    354 Print Tuesday, 24 June 2014 08:51 ALS Capabilities Reveal Multiple Functions of Ebola Virus ebola Researchers at the ALS have demonstrated that a protein of Ebola virus,...

  12. Patents -- Ivar Giaever (1976)

    Office of Scientific and Technical Information (OSTI)

    and separating select viruses, bacteria and other cells from multi-cell, bacteria or virus populations. US 3,975,238 METHOD AND APPARATUS FOR DETECTING MOLECULES IN SOLUTIONS --...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Structure of Hepatitis C Virus Envelope Glycoprotein E1 Antigenic Site 314-324 in Complex ... Structure of Hepatitis C Virus Envelope Glycoprotein E2 Antigenic Site 412-423 in Complex ...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Filter Results Filter by Subject aids virus (5) applied life sciences (4) cleavage (2) ... Resistance of a human immunodeficiency virus type 1 isolate to a small molecule CCR5 ...

  15. Microsoft Word - h1n1

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    The similarity of the Sa antigenic site, in particular, of the 2009 H1N1 virus with the ... viruses in vivo (4), and binds to the Sa antigenic site which is nearly identical in ...

  16. SN-03 Rate Hearing (7i) Files (ratecases/sn03)

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    for any problems that may occur. Although these documents have been scanned by BPA anti-virus software, BPA cannot guarantee the files are virus-free. Notes: Some directories may...

  17. Report for the Office of Scientific and Technical Information...

    Office of Scientific and Technical Information (OSTI)

    ... are also caused by prions, and not by a virus or any other conventional infectious agent. ... H5N1 Influenza H5N1 influenza is a subtype of the influenza A virus that causes "bird ...

  18. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structure and inhibition of EV-D68, a virus that causes respiratory illness in children ... glycan receptor analogues show that they bind into the 'canyon' on the virus surface. ...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... synthase promoter and cauliflower mosaic virus 35S promoter enhancer region) or tomato ... The E1 expression was increased more than two fold when the 5'-UTL of alfalfa mosaic virus ...

  20. Optimization of Acidothermus Celluloyticus Endoglucanase (E1...

    Office of Scientific and Technical Information (OSTI)

    synthase promoter and cauliflower mosaic virus 35S promoter enhancer region) or tomato ... The E1 expression was increased more than two fold when the 5'-UTL of alfalfa mosaic virus ...

  1. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... The expression and genetic immunization of chimeric fragment of Hantaan virus M and S ... It suggested that the chimeric gene of Hantaan virus containing G2 fragment of M segment ...

  2. ORNL-5904 DE82 C19734 ORNL-5904 Cootr»* No. W 7405-eng-2o

    Office of Scientific and Technical Information (OSTI)

    ... R.; Mitra, S. "Restriction Map of the Single-Stranded DNA Genome of Kilham Rat Virus ... of the Restriction of the Endogenous Virus of the RFMUn Mouse," p 255. Abstracts of ...

  3. Domain-level rocking motion within a polymerase that translocates...

    Office of Scientific and Technical Information (OSTI)

    An X-ray crystallographic structure is described for unliganded Vaccinia virus poly(A) ... Vaccinia virus poly(A) polymerase (VP55) is the only known polymerase that can translocate ...

  4. "Title","Speaker","Publication Date","OSTI Identifier","Report...

    Office of Scientific and Technical Information (OSTI)

    ... of the influenza virus clear enough to discover a key commonality among influenza strains. ...tes","English",,,,"2016-01-28T05:00:00Z" "Virus-based piezoelectric energy ...

  5. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... endospore and MS2 virus were determined as a function of face velocity and loading time. ... and filter quality for virus but was not statistically significant for spore filtration. ...

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Filter Results Filter by Subject aids virus (1) applied life sciences (1) atomic force ... first targets of human immunodeficiency virus type-1 (HIV-1) infection and in turn play ...

  7. Metagenomic analysis of planktonic microbial consortia from a...

    Office of Scientific and Technical Information (OSTI)

    ... % by MG- RAST, 0.1 % by Blast) and virus or plasmid (0.2 % by MG-RAST, 0.07 % by Blast). ... Virus and bacteriophage reads included assignments to Myoviridae, a type of Caudovirus, ...

  8. More Efficient Conversion of Water to Hydrogen Fuels | U.S. DOE...

    Office of Science (SC)

    Assembling nano-sized bioreactors from a hydrogen-producing enzyme and a virus protein ... The bioreactors are made of hydrogen-producing enzymes (green) within virus protein shells ...

  9. Seeing Matter at Atomic and Molecular Scales | U.S. DOE Office...

    Office of Science (SC)

    ... Potential Anticancer Agent Using an x-ray beamline, the 3-D structure has been solved for Seneca Valley Virus-001, a virus that attacks certain cancer cells without harming normal ...

  10. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structural basis for the antibody neutralization of Herpes simplex virus Lee, Cheng-Chung ... Glycoprotein D (gD) of Herpes simplex virus (HSV) binds to a host cell surface receptor, ...

  11. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... is described for unliganded Vaccinia virus poly(A) polymerase monomer (VP55), showing ... Vaccinia virus poly(A) polymerase (VP55) is the only known polymerase that can translocate ...

  12. Molecular Characterizations of Surface Proteins Hemagglutinin...

    Office of Scientific and Technical Information (OSTI)

    During 2014, a subclade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around the world. In late 2014early 2015, the virus was detected in ...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... three test and one reference delay lines was used to adsorb antibodies directed against Coxsackie virus B4 or the negative-stranded category A bioagent Sin Nombre virus (SNV). ...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structural Analysis of the Hemagglutinin from the Recent 2013 H7N9 Influenza Virus Yang, ... pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around the world. ...

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Access to the storage device is blocked by a kernel filter driver, except exclusive access is granted to a first anti-virus engine. The first anti-virus engine is directed to scan ...

  16. Architecture for removable media USB-ARM (Patent) | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Access to the storage device is blocked by a kernel filter driver, except exclusive access is granted to a first anti-virus engine. The first anti-virus engine is directed to scan ...

  17. Structural basis for the antibody neutralization of Herpes simplex...

    Office of Scientific and Technical Information (OSTI)

    of Herpes simplex virus Citation Details In-Document Search Title: Structural basis for the antibody neutralization of Herpes simplex virus The gD-E317-Fab complex ...

  18. Biogenic Aerosols Effects on Climate and Clouds Cloud OD Sensor...

    Office of Scientific and Technical Information (OSTI)

    ... Because of our direct connection to the Internet, virus software protection was installed and frequent virus scans were scheduled at night. 4.0 TWST Data Catalog TWST was deployed ...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... AAnn Arbor660 (AA ca) (H2N2) virus in mice and ferrets to evaluate its use in the event of an H2 influenza pandemic. The AA ca virus was restricted in replication in the ...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Functional analysis of miR-181a and Fas involved in hepatitis B virus-related ... The hepatitis B virus (HBV) is responsible for most of hepatocellular carcinoma (HCC). ...

  1. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Structure and Mutagenesis of the Parainfluenza Virus 5 Hemagglutinin-Neuraminidase Stalk ... Parainfluenza virus 5 (PIV5) HN exists as a noncovalent dimer-of-dimers on the surface of ...

  2. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... infection by blocking adsorption of the virus to the cells. * GLTA and GLTB bind to EV71 ... through interacting with the viral particle to block the adsorption of virus to the cells. ...

  3. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ...erazine-2-carboxamides to the hepatitis C virus polymerase Gentles, Robert G. ; Sheriff, ... These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and ...

  4. Molecular Characterizations of Surface Proteins Hemagglutinin and

    Office of Scientific and Technical Information (OSTI)

    Neuraminidase from Recent H5Nx Avian Influenza Viruses (Journal Article) | SciTech Connect Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses Citation Details In-Document Search Title: Molecular Characterizations of Surface Proteins Hemagglutinin and Neuraminidase from Recent H5Nx Avian Influenza Viruses During 2014, a subclade 2.3.4.4 highly pathogenic avian influenza (HPAI) A(H5N8) virus caused poultry outbreaks around

  5. Dr. Andrew Russo

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Disabling a Killer Virus The CAMD Protein Crystallography beamline was used to determine the structure of a protein that the Venezuelan Equine Encephalitis (VEE) virus requires for replication. VEE is a mosquito-borne virus found in Central and South America, and southern Texas. Periodic outbreaks infect tens of thousands of people and kill hundreds of thousands of horses, donkeys and mules. The virus was developed into a biological weapon during the Cold War by both the United States and the

  6. 2012 - 09 | Jefferson Lab

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    9 Sep 2012 Wed, 2012-09-26 15:00 JLab Computing: Microsoft Windows Patch Scheduled for Tonight Wed, 2012-09-26 15:00 Annual United Way Campaign Wed, 2012-09-26 15:00 Machine Shop Work Requests Wed, 2012-09-26 15:00 2012 Vacation Donation Open Enrollment Wed, 2012-09-19 15:00 Don't Use Internet Explorer Unless Necessary: Malware Found Wed, 2012-09-19 15:00 Change in JLab Pay Dates Wed, 2012-09-19 15:00 Performance Appraisal Process Begins 9/25/2012 Wed, 2012-09-12 15:00 Occ. Med. Offers Staff Flu

  7. 2015 - 09 | Jefferson Lab

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    9 Sep 2015 Wed, 2015-09-30 15:13 Performance Appraisal Process Underway; Began on 9/30/2015 Wed, 2015-09-30 08:30 Message from Hugh Montgomery: All-Hands Meeting on Oct. 1 Wed, 2015-09-30 08:22 Jefferson Lab to Test Tornado Warning Siren at 10:30 a.m. on Friday, Oct. 2 Tue, 2015-09-29 12:20 October Blood Drive Announcement Mon, 2015-09-28 15:15 JLab Vacation Donation Program Open Enrollment Mon, 2015-09-28 15:13 Occ. Med. Offers Staff Flu Vaccines by Appointment Mon, 2015-09-28 15:03 2015 United

  8. Design Construction and Operation of a Supercritical Carbon Dioxide (sCO2) Loop for Investigation of Dry Cooling and Natural Circulation Potential for Use in Advanced Small Modular Reactors Utilizing sCO2 Power Conversion Cycles.

    SciTech Connect

    Middleton, Bobby D.; Rodriguez, Salvador B.; Carlson, Matthew David

    2015-11-01

    This report outlines the work completed for a Laboratory Directed Research and Development project at Sandia National Laboratories from October 2012 through September 2015. An experimental supercritical carbon dioxide (sCO 2 ) loop was designed, built, and o perated. The experimental work demonstrated that sCO 2 can be uti lized as the working fluid in an air - cooled, natural circulation configuration to transfer heat from a source to the ultimate heat sink, which is the surrounding ambient environment in most ca ses. The loop was also operated in an induction - heated, water - cooled configuration that allows for measurements of physical parameters that are difficult to isolate in the air - cooled configuration. Analysis included the development of two computational flu id dynamics models. Future work is anticipated to answer questions that were not covered in this project.

  9. Interim Report on Multiple Sequence Alignments and TaqMan Signature Mapping to Phylogenetic Trees

    SciTech Connect

    Gardner, S; Jaing, C

    2012-03-27

    The goal of this project is to develop forensic genotyping assays for select agent viruses, addressing a significant capability gap for the viral bioforensics and law enforcement community. We used a multipronged approach combining bioinformatics analysis, PCR-enriched samples, microarrays and TaqMan assays to develop high resolution and cost effective genotyping methods for strain level forensic discrimination of viruses. We have leveraged substantial experience and efficiency gained through year 1 on software development, SNP discovery, TaqMan signature design and phylogenetic signature mapping to scale up the development of forensics signatures in year 2. In this report, we have summarized the Taqman signature development for South American hemorrhagic fever viruses, tick-borne encephalitis viruses and henipaviruses, Old World Arenaviruses, filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus and Japanese encephalitis virus.

  10. Forecasting the 2013–2014 influenza season using Wikipedia

    DOE PAGES [OSTI]

    Hickmann, Kyle S.; Fairchild, Geoffrey; Priedhorsky, Reid; Generous, Nicholas; Hyman, James M.; Deshpande, Alina; Del Valle, Sara Y.; Salathé, Marcel

    2015-05-14

    Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are appliedmore » to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.« less

  11. Forecasting the 2013–2014 influenza season using Wikipedia

    SciTech Connect

    Hickmann, Kyle S.; Fairchild, Geoffrey; Priedhorsky, Reid; Generous, Nicholas; Hyman, James M.; Deshpande, Alina; Del Valle, Sara Y.; Salathé, Marcel

    2015-05-14

    Infectious diseases are one of the leading causes of morbidity and mortality around the world; thus, forecasting their impact is crucial for planning an effective response strategy. According to the Centers for Disease Control and Prevention (CDC), seasonal influenza affects 5% to 20% of the U.S. population and causes major economic impacts resulting from hospitalization and absenteeism. Understanding influenza dynamics and forecasting its impact is fundamental for developing prevention and mitigation strategies. We combine modern data assimilation methods with Wikipedia access logs and CDC influenza-like illness (ILI) reports to create a weekly forecast for seasonal influenza. The methods are applied to the 2013-2014 influenza season but are sufficiently general to forecast any disease outbreak, given incidence or case count data. We adjust the initialization and parametrization of a disease model and show that this allows us to determine systematic model bias. In addition, we provide a way to determine where the model diverges from observation and evaluate forecast accuracy. Wikipedia article access logs are shown to be highly correlated with historical ILI records and allow for accurate prediction of ILI data several weeks before it becomes available. The results show that prior to the peak of the flu season, our forecasting method produced 50% and 95% credible intervals for the 2013-2014 ILI observations that contained the actual observations for most weeks in the forecast. However, since our model does not account for re-infection or multiple strains of influenza, the tail of the epidemic is not predicted well after the peak of flu season has passed.

  12. Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells

    SciTech Connect

    Saito, Kousuke; Saito, Mineki; Taniura, Naoko; Okuwa, Takako; Ohara, Yoshiro

    2010-08-01

    Bcl3 is a member of the I{kappa}B family that regulates genes involved in cell proliferation and apoptosis. Recent reports indicated that Bcl3 is overexpressed in HTLV-1-infected T cells via Tax-mediated transactivation, and acts as a negative regulator of viral transcription. However, the role of Bcl3 in cellular signal transduction and the growth of HTLV-1-infected T cells have not been reported. In this study, we showed that the knockdown of Bcl3 by short hairpin RNA inhibited the growth of HTLV-1-infected T cells. Although phosphatidylinositol-3 kinase (PI3K) inhibitor reduced Bcl3 expression, inactivation of glycogen synthase kinase 3 (GSK3), an effector kinase of the PI3K/Akt signaling pathway, restored Bcl3 expression in Tax-negative but not in Tax-positive T cells. Our results indicate that the overexpression of Bcl3 in HTLV-1-infected T cells is regulated not only by transcriptional but also by post-transcriptional mechanisms, and is involved in overgrowth of HTLV-1-infected T cells.

  13. Architecture for removable media USB-ARM

    SciTech Connect

    Shue, Craig A.; Lamb, Logan M.; Paul, Nathanael R.

    2015-07-14

    A storage device is coupled to a computing system comprising an operating system and application software. Access to the storage device is blocked by a kernel filter driver, except exclusive access is granted to a first anti-virus engine. The first anti-virus engine is directed to scan the storage device for malicious software and report results. Exclusive access may be granted to one or more other anti-virus engines and they may be directed to scan the storage device and report results. Approval of all or a portion of the information on the storage device is based on the results from the first anti-virus engine and the other anti-virus engines. The storage device is presented to the operating system and access is granted to the approved information. The operating system may be a Microsoft Windows operating system. The kernel filter driver and usage of anti-virus engines may be configurable by a user.

  14. A bio-synthetic interface for discovery of viral entry mechanisms.

    SciTech Connect

    Gutzler, Mike; Maar, Dianna; Negrete, Oscar; Hayden, Carl C.; Sasaki, Darryl Yoshio; Stachowiak, Jeanne C.; Wang, Julia

    2010-09-01

    Understanding and defending against pathogenic viruses is an important public health and biodefense challenge. The focus of our LDRD project has been to uncover the mechanisms enveloped viruses use to identify and invade host cells. We have constructed interfaces between viral particles and synthetic lipid bilayers. This approach provides a minimal setting for investigating the initial events of host-virus interaction - (i) recognition of, and (ii) entry into the host via membrane fusion. This understanding could enable rational design of therapeutics that block viral entry as well as future construction of synthetic, non-proliferating sensors that detect live virus in the environment. We have observed fusion between synthetic lipid vesicles and Vesicular Stomatitis virus particles, and we have observed interactions between Nipah virus-like particles and supported lipid bilayers and giant unilamellar vesicles.

  15. LOS ALAMOS, N.M., Nov. 19, 2013-Researchers at Los Alamos National Laboratory

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    virus spread and evolution studied through computer modeling November 19, 2013 LOS ALAMOS, N.M., Nov. 19, 2013-Researchers at Los Alamos National Laboratory are investigating the complex relationships between the spread of the HIV virus in a population (epidemiology) and the actual, rapid evolution of the virus (phylogenetics) within each patient's body. "We have developed novel ways of estimating epidemics dynamics such as who infected whom, and the true population incidence of infection

  16. Self-assembled Ni/TiO{sub 2} nanocomposite anodes synthesized...

    Office of Scientific and Technical Information (OSTI)

    Ni(core)TiOsub 2(shell) nanocomposite anodes were fabricated on three-dimensional, self-assembled nanotemplates of Tobacco mosaic virus using atomic layer deposition, exhibiting ...

  17. Nanomaterial Composites for Next Generation Water Filters: Cooperative Research and Development Final Report, CRADA Number CRD-06-197

    SciTech Connect

    Ginley, D.

    2013-04-01

    Under this CRADA, the Parties will produce and test a composite filter element that will remove particles, bacteria and viruses to produce safe drinking water.

  18. SC e-journals by Publisher

    Office of Scientific and Technical Information (OSTI)

    ... and Archaeobotany Veterinary Research Communications Virchows Archiv Virtual Reality Virus Genes Visual Computer, The Visual Geosciences VLDB Journal, The Water, Air, and Soil ...

  19. SEQUEDEX

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    diseases (whether arising from bacteria, parasites, or viruses; characterizing gut, oral and skin microbiomes of humans, livestock, and pets; metagenomics of soils, rivers,...

  20. ALSNews Vol. 338

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    aid in the eventual development of a universal vaccine, protecting against all types of influenza viruses and eliminating the guesswork that limits vaccine effectiveness. Read...

  1. Human Genome Research: Decoding DNA

    Office of Scientific and Technical Information (OSTI)

    ... Speeding Up the Process of Gene Discovery Engineered Enzyme Accelerates DNA Sequencing Putting a Virus to Practical Use DOE Joint Genome Institute The Human Genome Project: ...

  2. Slide 1

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    June 15, 2010 2 West Nile Virus - Awareness * Hanford All Employee bulletins * Presidents' Zero Accident Council (PZAC) meeting attendance * AdvanceMed Hanford information links * ...

  3. 1

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Under scrutiny is the virus's putative link with a congenital birth defect called microcephaly, which causes babies to be born with abnormally small heads and undeveloped brains. ...

  4. Why is Zika now a threat?

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Under scrutiny is the virus's putative link with a congenital birth defect called microcephaly, which causes babies to be born with abnormally small heads and undeveloped brains. ...

  5. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... USDOE Office of Civilian Radioactive Waste Management (RW) (United States) USDOE Office of ... virus for micro-supercapacitors in solid Nafion electrolyte Gnerlich, Markus ; ...

  6. Discovery and Preclinical Characterization of theCyclopropylindoloben...

    Office of Scientific and Technical Information (OSTI)

    clopropylindolobenzazepine BMS-791325, A Potent Allosteric Inhibitor of the Hepatitis C Virus NS5B Polymerase Citation Details In-Document Search Title: Discovery and Preclinical...

  7. EA-1363: Finding of No Significant Impact

    Energy.gov [DOE]

    Joint Environmental Assessment 2002-2006 of the California Department Of Food and Agriculture Curly Top Virus Control Program for Bureau Of Land Management and Department Of Energy

  8. C:\\Users\\28105\\Documents\\Choi ICF\\ESPA-LPT work\\RFI\\PDF Conversions...

    Energy.gov [DOE] (indexed site)

    ... our US Contacts Page (accessed by clicking on the appropriate link) Please ensure you have adequate virus protection before you open or detach any documents from this transmission. ...

  9. Ectopic expression of anti-HIV-1 shRNAs protects CD8{sup +} T...

    Office of Scientific and Technical Information (OSTI)

    ... Country of Publication: United States Language: English Subject: 60 APPLIED LIFE SCIENCES; AIDS VIRUS; ANTIGENS; CELL PROLIFERATION; IMMUNOTHERAPY; IN VITRO; IN VIVO; INSPECTION; ...

  10. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... By separating the diffraction pattern of the virus particles from that of their surroundings, we performed quantitative and high-contrast imaging of a single virion. The structure ...

  11. WHERE MULTIFUNCTIONAL DNA REPAIR PROTEINS MEET: MAPPING THE INTERACTIO...

    Office of Scientific and Technical Information (OSTI)

    ... As a graduate student, she studied the interactions between proteins required for Herpes simplex virus DNA replication. Following graduation, Dr. Trego was a postdoctoral fellow in ...

  12. "Title","Creator/Author","Publication Date","OSTI Identifier...

    Office of Scientific and Technical Information (OSTI)

    developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were...

  13. disease outbreak. Brozik, Susan Marie; Manginell, Ronald Paul...

    Office of Scientific and Technical Information (OSTI)

    developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. Both optical and electrochemical transduction technologies were...

  14. TITLE AUTHORS SUBJECT SUBJECT RELATED DESCRIPTION PUBLISHER AVAILABILI...

    Office of Scientific and Technical Information (OSTI)

    assays developed in goal We generated and characterized suitable primers for West Nile Virus RNA detection Both optical and electrochemical transduction technologies were...

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    of Ligands Targeting a Novel Site on the Integrase Enzyme of Human Immunodeficiency Virus;8197;1 Wielens, Jerome ; Headey, Stephen J. ; Deadman, John J. ; Rhodes, David I. ;...

  16. Inspection Report: IG-0492 | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) (indexed site)

    Biological select agents include about 40 viruses, bacteria, rickettsia, fungi, and toxins whose transfer within the United States is controlled. This is because such agents pose a ...

  17. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... changes (2) crystal structure (2) materials science (2) proteins (2) affinity (1) aids virus (1) biology (1) carcinomas (1) catalysis (1) chemical shift (1) cross-linking (1) ...

  18. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Centralized, blinded histology on the graft was used to classify matched urine samples into categories of acute rejection (AR), chronic allograft nephropathy (CAN), BK virus ...

  19. SC e-journals, Medicine

    Office of Scientific and Technical Information (OSTI)

    ... Trends in Microbiology Veterinary Research Communications Virchows Archiv Virology Virtual Journal of Biomedical Optics Virus Genes X-Ray Spectrometry Zeitschrift fr Kardiologie

  20. SC e-journals, Biology/Genetics

    Office of Scientific and Technical Information (OSTI)

    ... Research Communications Virchows Archiv Virology Virtual Journal of Biomedical Optics Virus Genes Water Resources Water Resources Management Water Resources Research Wetlands ...

  1. CPL4001840-20151231100208

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    este mensaje, ni se responsabiliza de los posibles perjuicios de cualquier naturaleza derivados de la captura de datos, virus informaticos o manipulaciones efectuadas por terceros....

  2. ALSNews Vol. 332

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Structured Biomimetic Materials biomemetic materials Researchers have turned a benign virus into an engineering tool for assembling structures that mimic collagen, one of the...

  3. Link Alpha A

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Alvarez Physics Memos AmeriFlux Animal Welfare and Research Committee (AWRC) Anti-virus software Apartment Retrofits for Energy and Indoor Environmental Quality (IEQ)...

  4. Science On Tap - Phylogenetics and Epidemics

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    and the actual, rapid evolution of the virus (phylogenetics) within each patient's body. "We have developed novel ways of estimating epidemics dynamics such as who infected...

  5. LOS ALAMOS, N.M., Nov. 19, 2013-Researchers at Los Alamos National...

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    and the actual, rapid evolution of the virus (phylogenetics) within each patient's body. "We have developed novel ways of estimating epidemics dynamics such as who infected...

  6. Superhydrophobic surfaces (Patent) | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    The hierarchical surfaces can be fabricated using biological nanostructures, such as viruses as a self-assembled nanoscale template. Authors: Wang, Evelyn N ; McCarthy, Matthew ; ...

  7. Sandia, UCLA develop screening libraries to discover drug targets...

    National Nuclear Security Administration (NNSA)

    As headlines highlight the threat of viruses like Ebola and Zika, researchers at Sandia National Laboratories and the University of California Los Angeles (UCLA) have teamed up to ...

  8. The FELICIA bulletin board system and the IRBIS anonymous FTP server: Computer security information sources for the DOE community. CIAC-2302

    SciTech Connect

    Orvis, W.J.

    1993-11-03

    The Computer Incident Advisory Capability (CIAC) operates two information servers for the DOE community, FELICIA (formerly FELIX) and IRBIS. FELICIA is a computer Bulletin Board System (BBS) that can be accessed by telephone with a modem. IRBIS is an anonymous ftp server that can be accessed on the Internet. Both of these servers contain all of the publicly available CIAC, CERT, NIST, and DDN bulletins, virus descriptions, the VIRUS-L moderated virus bulletin board, copies of public domain and shareware virus- detection/protection software, and copies of useful public domain and shareware utility programs. This guide describes how to connect these systems and obtain files from them.

  9. ALSNews Vol. 359

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    JavaScript enabled to view it Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Researchers used new protein design approaches to develop a potential inhibitor of...

  10. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structure of the cleavage-activated prefusion form of the parainfluenza virus 5 fusion protein Welch, Brett D. ; Liu, Yuanyuan ; Kors, Christopher A. ; Leser, George P. ; ...

  11. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... ligand, (2) the optimized nuclear localization sequence of simian vacuolating virus 40 (SV40) large T-antigen, (3) a translocation domain of diphtheria toxin as an ...

  12. High level expression of Acidothermus cellulolyticus β-1, 4...

    Office of Scientific and Technical Information (OSTI)

    The expression of the bacterial gene in rice was driven by the constitutive Mac promoter, a hybrid promoter of Ti plasmid mannopine synthetase promoter and cauliflower mosaic virus ...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... cauliflower mosaic virus 35S promoter enhancer with the signal peptide of tobacco pathogenesis-related protein for targeting the protein to the apoplastic compartment for storage. ...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Ritonavir (RTV), a human immunodeficiency virus (HIV) protease inhibitor, induces atherosclerosis in an estrogen-related manner. However, how RTV induce pathological phenotypes ...

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structural Studies of Chikungunya Virus-Like Particles Complexed with Human Antibodies: Neutralization and Cell-to-Cell Transmission Porta, Jason ; Prasad, Vidya Mangala ; Wang, ...

  16. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Structure of Red clover necrotic mosaic virus probed by Small Angle Neutron Scattering Martin, S. L. ; He, Lilin ; Meilleur, Flora ; Guenther, Richard ; Sit, Tim L. ; Lommel, ...

  17. Calendar Year 2001 | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) (indexed site)

    of the Purchase of Protective Force Respirators April 5, 2001 Audit Report: IG-0500 Virus Protection Strategies and Cyber Security Incident Reporting April 3, 2001 Special...

  18. Project 3: Pond Crash Forensics

    Office of Energy Efficiency and Renewable Energy (EERE) (indexed site)

    ... diagnostics: SpinDX - Sandia's hyperspectral imaging capabilities. 1-Approach ... of the Chlorella Virus PBCV-1 with Hyperspectral Confocal Microscopy", presented at ...

  19. Using XAFS to Determine Origin of Ferromagnetism in LaCoO3 | Stanford

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Using X-Rays to Zap the Zika Virus Using X-Rays to Zap the Zika Virus July 29, 2016 - 2:55pm Addthis New knowledge about the Zika Virus gets us closer to finding effective treatment. | Video by Argonne National Laboratory. Pat Adams Pat Adams Digital Content Specialist, Office of Public Affairs The Zika virus is a growing public health crisis. We don't yet have a vaccine or drug treatment to combat the spreading problem, but a team of researchers just got a big step closer. Researchers from the

  20. Work with Biological Materials

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    cells, viruses), plant or soil samples (USDA quarantines), recombinant DNA, or blood-borne pathogen. Biological Use Authorization The great majority of biological work at...

  1. Closer to HIV vaccine goal with new insight into viral factors

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    donor's predominant virus subpopulation in the genital tract differed from that in the blood. Comparing the HIV sequence population in each newly infected partner with that in the...

  2. BSL Fact Sheet_r02_12-08-2005_keb.pub

    National Nuclear Security Administration (NNSA)

    virus, severe acute respiratory syndrome (SARS), monkeypox, and annual outbreaks of influenza. To control epidemics and protect the public health, medical researchers must...

  3. February | U.S. DOE Office of Science (SC)

    Office of Science (SC)

    ... String searching is at the core of many security and network applications such as search engines, intrusion detection systems, virus scanners and spam filters. PNNL researchers are ...

  4. Science Highlights | U.S. DOE Office of Science (SC)

    Office of Science (SC)

    ... More Efficient Conversion of Water to Hydrogen Fuels Assembling nano-sized bioreactors from a hydrogen-producing enzyme and a virus protein shell increases enzyme stability and ...

  5. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter. ...

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... platforms for preclinical and field testing that utilize the assays developed in goal 1. We generated and characterized suitable primers for West Nile Virus RNA detection. ...

  7. January 2013 Most Viewed Documents for Biology And Medicine ...

    Office of Scientific and Technical Information (OSTI)

    metropolitana de Sao Paulo, Brasil, utilizando a bromelia Tillandsia usneoides L. como biomonitor Nogueira, Claudio Ailton Development of simulation tools for virus shell assembly. ...

  8. In the OSTI Collections: Microfluidics | OSTI, US Dept of Energy...

    Office of Scientific and Technical Information (OSTI)

    ... Figure 2. Schematic and "photographic" depictions of a typical multidimensional separation using modular microfluidics on an aqueous virus sample. (From "Multidimensional ...

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Track Viral Evolution - A sensitive technique developed at the Laboratory can identify virus mutations that may jump frommore host to host; and (5) Data for Defense: New ...

  10. NNSA Product Aids in Anthrax Clean-up

    National Nuclear Security Administration (NNSA)

    development project funded by NNSA's Chemical and Biological National Security Program. ... was effective against chemical warfare agents, toxins, viruses and anthrax spores. ...

  11. 1

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Stopping executions, saving computers with new malware detection tool October 21, 2009 Virus detection takes a smarter turn with information- based approach Los Alamos, New Mexico,...

  12. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... sciences (2) basic biological sciences (2) hydrogen (2) acrolein (1) adducts (1) aids virus (1) animal cells (1) antibodies (1) arginine (1) biological radiation effects (1) ...

  13. Investigation of type-I interferon dysregulation by arenaviruses...

    Office of Scientific and Technical Information (OSTI)

    infection assays, molecular virology analysis of Arenavirus nucleoprotein structure-function, and development of computational tools to predict virus-host protein interactions. ...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... (2) quantum mechanics (2) qubits (2) transmission electron microscopy (2) aids virus (1) air pollution control (1) animal cells (1) anisotropy (1) antibodies (1) ...

  15. Broad Distribution of Energetically Important Contacts across...

    Office of Scientific and Technical Information (OSTI)

    Language: ENGLISH Subject: 59 BASIC BIOLOGICAL SCIENCES; 60 APPLIED LIFE SCIENCES; AFFINITY; AIDS VIRUS; DISTRIBUTION; HYPOTHESIS; PROTEINS Word Cloud More Like This Full Text ...

  16. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... analytical chemistry (2) photon-molecule collisions (2) pulses (2) velocity (2) aids virus (1) ammonia (1) anisotropy (1) apoptosis (1) applied life sciences (1) arteriosclerosis ...

  17. Microsoft Word - pfam5000_revised.doc

    Office of Scientific and Technical Information (OSTI)

    ... The mean subfamily size is 8, and the largest subfamily, from the Pfam family HVCcapsid (hepatitis C virus capsid protein), contains 1236 sequences. 15 Figure 7: Number of ...

  18. Selective deposition of nanostructured ruthenium oxide using...

    Office of Scientific and Technical Information (OSTI)

    This content will become publicly available on June 5, 2017 Title: Selective deposition of nanostructured ruthenium oxide using Tobacco mosaic virus for micro-supercapacitors in ...

  19. Modular microfluidic system for biological sample preparation...

    Office of Scientific and Technical Information (OSTI)

    module, c) a dielectrophoresis virus filter module, d) an isotachophoresis nucleic acid filter module, e) a lyses module, and f) an isotachophoresis-based nucleic acid filter. ...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Structure-Function Analysis of Vaccinia Virus H7 Protein Reveals a Novel Phosphoinositide Binding Fold Essential for Poxvirus Replication Kolli, Swapna ; Meng, Xiangzhi ; Wu, Xiang ...

  1. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Filter Results Filter by Subject chem (3) applied life sciences (2) basic biological sciences (2) design (2) glycoproteins (2) affinity (1) aids virus (1) antibodies (1) antigens ...

  2. HIV evolution in early infection: selection pressures, patterns...

    Office of Scientific and Technical Information (OSTI)

    host environment and immune responses typically experienced by the newly transmitted virus. For example, sites that tend to evolve rapidly across multiple early-infection...

  3. Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser

    DOE Data Explorer

    Ekeberg, Tomas

    2015-05-26

    This dataset contains the diffraction patterns that were used for the first three-dimensional reconstruction of a virus using FEL data. The sample was the giant mimivirus particle, which is one of the largest known viruses with a diameter of 450 nm. The dataset consists of the 198 diffraction patterns that were used in the analysis.

  4. TYLCV-Is movement in planta does not require V2 protein

    SciTech Connect

    Hak, Hagit; Levy, Yael; Chandran, Sam A.; Belausov, Eduard; Loyter, Abraham; Lapidot, Moshe; Gafni, Yedidya

    2015-03-15

    Tomato yellow leaf curl virus (TYLCV), a major tomato pathogen causing extensive crop losses, is a whitefly-transmitted geminivirus. V2 mutants of TYLCV-Is and related viruses tend to induce symptomless infection with attenuated viral DNA levels, while accumulating close to wild-type DNA levels in protoplasts, suggesting V2 as a movement protein. The discovery of plant-silencing mechanisms and viral silencing suppressors, V2 included, led us to reconsider V2's involvement in viral movement. We studied two mutant versions of the virus, one impaired in V2 silencing-suppression activity, and another carrying a non-translatable V2. While both mutant viruses spread in the infected plant to newly emerged leaves at the same rate as the wild-type virus, their DNA-accumulation levels were tenfold lower than in the wild-type virus. Thus, we suggest that the setback in virus proliferation, previously ascribed to a movement impediment, is due to lack of silencing-suppression activity. - Highlights: • TYLCV-Is V2 protein is localized in distinct microbodies throughout the cell cytoplasm, around the nucleus and in association with cytoplasmic strands but is not associated with the plasmodesmata. • Disruption of RNA-silencing suppression activity of TYLCV-Is V2 protein causes low titer of the virus in the infected plants. • The movement of TYLCV-Is in planta does not require a functional V2 protein.

  5. Viral chemotherapy. Volume 2

    SciTech Connect

    Shugar, D.

    1985-01-01

    This book contains seven chapters. Some of the chapter titles are: Molecular aspects of RNA tumor virus-induced carcinogenesis; Trifluorothymidine; Effects of antiviral nucleoside analogs on purine metabolism; Development of drug resistance and dependence in viruses; and Low molecular weight interferon inducers: Structure and biology.

  6. Anti-influenza M2e antibody

    DOEpatents

    Bradbury, Andrew M.

    2011-12-20

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  7. Anti-influenza M2e antibody

    DOEpatents

    Bradbury, Andrew M.

    2013-04-16

    Humanized recombinant and monoclonal antibodies specific for the ectodomain of the influenza virus M2 ion channel protein are disclosed. The antibodies of the invention have anti-viral activity and may be useful as anti-viral therapeutics and/or prophylactic/vaccine agents for inhibiting influenza virus replication and for treating individuals infected with influenza.

  8. Detection of bioagents using a shear horizontal surface acoustic wave biosensor

    DOEpatents

    Larson, Richard S; Hjelle, Brian; Hall, Pam R; Brown, David C; Bisoffi, Marco; Brozik, Susan M; Branch, Darren W; Edwards, Thayne L; Wheeler, David

    2014-04-29

    A biosensor combining the sensitivity of surface acoustic waves (SAW) generated at a frequency of 325 MHz with the specificity provided by antibodies and other ligands for the detection of viral agents. In a preferred embodiment, a lithium tantalate based SAW transducer with silicon dioxide waveguide sensor platform featuring three test and one reference delay lines was used to adsorb antibodies directed against Coxsackie virus B4 or the negative-stranded category A bioagent Sin Nombre virus (SNV). Rapid detection of increasing concentrations of viral particles was linear over a range of order of magnitude for both viruses, and the sensor's selectivity for its target was not compromised by the presence of confounding Herpes Simplex virus type 1 The biosensor was able to delect SNV at doses lower than the load of virus typically found in a human patient suffering from hantavirus cardiopulmonary syndrome (HCPS).

  9. Economic and policy implications of pandemic influenza.

    SciTech Connect

    Smith, Braeton J.; Starks, Shirley J.; Loose, Verne W.; Brown, Theresa Jean; Warren, Drake E.; Vargas, Vanessa N.

    2010-03-01

    Pandemic influenza has become a serious global health concern; in response, governments around the world have allocated increasing funds to containment of public health threats from this disease. Pandemic influenza is also recognized to have serious economic implications, causing illness and absence that reduces worker productivity and economic output and, through mortality, robs nations of their most valuable assets - human resources. This paper reports two studies that investigate both the short- and long-term economic implications of a pandemic flu outbreak. Policy makers can use the growing number of economic impact estimates to decide how much to spend to combat the pandemic influenza outbreaks. Experts recognize that pandemic influenza has serious global economic implications. The illness causes absenteeism, reduced worker productivity, and therefore reduced economic output. This, combined with the associated mortality rate, robs nations of valuable human resources. Policy makers can use economic impact estimates to decide how much to spend to combat the pandemic influenza outbreaks. In this paper economists examine two studies which investigate both the short- and long-term economic implications of a pandemic influenza outbreak. Resulting policy implications are also discussed. The research uses the Regional Economic Modeling, Inc. (REMI) Policy Insight + Model. This model provides a dynamic, regional, North America Industrial Classification System (NAICS) industry-structured framework for forecasting. It is supported by a population dynamics model that is well-adapted to investigating macro-economic implications of pandemic influenza, including possible demand side effects. The studies reported in this paper exercise all of these capabilities.

  10. I Am Science - and So Can You!

    SciTech Connect

    DiChristina, Mariette

    2013-05-08

    Science is humanity’s best invention for getting at the truth about how things work (a.k.a. “basic research”) and solving problems (“applied”). I can even make a claim that most people are interested in science topics—they just don’t think of them as “science.” Consider how many of today’s top headlines have a critical science underpinning: energy supply, social change from digital innovations, efforts to treat cancer and other diseases, emerging infectious agents like bird flu, climate change, and so on. Clearly, a basic understanding about science is more vital than ever. At the same time, we see two trends: the collapse of traditional science journalism jobs as newspapers have cut thousands of positions and a greater access to—and a larger readership for—science-related materials than the world has ever known. Put another way, just when the public needs the Fourth Estate most, it’s instead drowning in a sea of 24/7 misinformation (a.k.a. “the Internet”). What’s a busy scientist to do to help engage the lay public? Glad you asked.

  11. Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

    DOE PAGES [OSTI]

    Gardner, Shea N.; Jaing, Crystal J.; Elsheikh, Maher M.; Peña, José; Hysom, David A.; Borucki, Monica K.

    2014-01-01

    Background . Targeted enrichment improves coverage of highly mutable viruses at low concentration in complex samples. Degenerate primers that anneal to conserved regions can facilitate amplification of divergent, low concentration variants, even when the strain present is unknown. Results . A tool for designing multiplex sets of degenerate sequencing primers to tile overlapping amplicons across multiple whole genomes is described. The new script, run_tiled_primers, is part of the PriMux software. Primers were designed for each segment of South American hemorrhagic fever viruses, tick-borne encephalitis, Henipaviruses, Arenaviruses, Filoviruses, Crimean-Congo hemorrhagic fever virus, Rift Valley fever virus, and Japanese encephalitis virus.more » Each group is highly diverse with as little as 5% genome consensus. Primer sets were computationally checked for nontarget cross reactions against the NCBI nucleotide sequence database. Primers for murine hepatitis virus were demonstrated in the lab to specifically amplify selected genes from a laboratory cultured strain that had undergone extensive passage in vitro and in vivo. Conclusions . This software should help researchers design multiplex sets of primers for targeted whole genome enrichment prior to sequencing to obtain better coverage of low titer, divergent viruses. Applications include viral discovery from a complex background and improved sensitivity and coverage of rapidly evolving strains or variants in a gene family.« less

  12. Characterization of a novel insect-specific flavivirus from Brazil: Potential for inhibition of infection of arthropod cells with medically important flaviviruses.

    DOE PAGES [OSTI]

    Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.; Brault, Aaron C.

    2014-01-12

    In the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated ‘Nhumirim virus’; NHUV) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential and 3' untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp.-vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell linesmore » were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3' UTR indicated NHUV to be most similar to viruses within the yellow fever serogroup and Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared with traditional insect-specific flaviviruses. This suggests that, despite apparently being insect specific, this virus probably diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a significant reduction in virus production of West Nile virus (WNV), St Louis encephalitis virus (SLEV) and Japanese encephalitis virus. As a result, the inhibitory effect was most effective against WNV and SLEV with over a 106-fold and 104-fold reduction in peak titres, respectively.« less

  13. Characterization of a novel insect-specific flavivirus from Brazil: Potential for inhibition of infection of arthropod cells with medically important flaviviruses.

    SciTech Connect

    Kenney, Joan L.; Solberg, Owen D.; Langevin, Stanley A.; Brault, Aaron C.

    2014-01-12

    In the past decade, there has been an upsurge in the number of newly described insect-specific flaviviruses isolated pan-globally. We recently described the isolation of a novel flavivirus (tentatively designated ‘Nhumirim virus’; NHUV) that represents an example of a unique subset of apparently insect-specific viruses that phylogenetically affiliate with dual-host mosquito-borne flaviviruses despite appearing to be limited to replication in mosquito cells. We characterized the in vitro growth potential and 3' untranslated region (UTR) sequence homology with alternative flaviviruses, and evaluated the virus’s capacity to suppress replication of representative Culex spp.-vectored pathogenic flaviviruses in mosquito cells. Only mosquito cell lines were found to support NHUV replication, further reinforcing the insect-specific phenotype of this virus. Analysis of the sequence and predicted RNA secondary structures of the 3' UTR indicated NHUV to be most similar to viruses within the yellow fever serogroup and Japanese encephalitis serogroup, and viruses in the tick-borne flavivirus clade. NHUV was found to share the fewest conserved sequence elements when compared with traditional insect-specific flaviviruses. This suggests that, despite apparently being insect specific, this virus probably diverged from an ancestral mosquito-borne flavivirus. Co-infection experiments indicated that prior or concurrent infection of mosquito cells with NHUV resulted in a significant reduction in virus production of West Nile virus (WNV), St Louis encephalitis virus (SLEV) and Japanese encephalitis virus. As a result, the inhibitory effect was most effective against WNV and SLEV with over a 106-fold and 104-fold reduction in peak titres, respectively.

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Everything17 Electronic Full Text0 Citations17 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject proteins (4) basic biological sciences (3) aids virus (2) applied ...

  15. Paul D. Boyer, Adenosine Triphosphate (ATP), and the Binding...

    Office of Scientific and Technical Information (OSTI)

    ... National Museum of American History A Conversation with UCLA Professor Emeritus Paul D. Boyer Paul D. Boyer Hall Patent: US 7,560,117; Foamy Virus Mutant Reverse Transcriptase

  16. Investigation of the mode of binding of a novel series ofN-benzyl...

    Office of Scientific and Technical Information (OSTI)

    of the hepatitis C viral polymerase are described herein. These compounds bind to the hepatitis C virus non-structural protein 5B (NS5B), and co-crystal structures of select...

  17. Validating Computer-Designed Proteins for Vaccines

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    Computed As strange as it sounds, most vaccines are composed of actual dead viruses and bacteria. The idea is that presenting a dead form of the pathogen will fake your body into...

  18. ORISE: Postdoctoral Research Experiences - Zaheer Ahmed

    U.S. Department of Energy (DOE) - all webpages (Extended Search)

    to train and research in different labs around the world including those in Hong Kong, Egypt, the United Kingdom, and Italy. "We were able to control the influenza virus in...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... These permuted enzymes are widespread in virus, pathogenic bacteria, and eukaryotes. We determined the crystal structure of a member of the YaeFYiiX-like family from Bacillus ...

  20. CoverSheet

    Office of Scientific and Technical Information (OSTI)

    that would be inappropriate and ineffective. For example, it seems likely that anti-virus tools will be a required compo- nent of the cyber health report scorecard for desktop...