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Sample records for outsmarting flu viruses

  1. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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 ...

  2. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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. Avian Flu

    SciTech Connect (OSTI)

    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.

  4. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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 economic burdens, but the highly changeable nature of the flu virus complicates the production of an effective vaccine. The Centers for Disease Control and Prevention (CDC) estimates that the effectiveness of this year's flu vaccine is about 62%. For comparison, this number for childhood vaccines is routinely well over

  5. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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 complicates the production of an effective vaccine. The Centers for Disease Control and Prevention (CDC) estimates that the effectiveness of this year's flu vaccine is about 62%. For comparison, this number for childhood vaccines is routinely well over 90%. One factor in determining the vaccine's effectiveness is how closely

  6. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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 complicates the production of an effective vaccine. The Centers for Disease Control and Prevention (CDC) estimates that the effectiveness of this year's flu vaccine is about 62%. For comparison, this number for childhood vaccines is routinely well over 90%. One factor in determining the vaccine's effectiveness is how closely

  7. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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 complicates the production of an effective vaccine. The Centers for Disease Control and Prevention (CDC) estimates that the effectiveness of this year's flu vaccine is about 62%. For comparison, this number for childhood vaccines is routinely well over 90%. One factor in determining the vaccine's effectiveness is how closely

  8. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  9. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office 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,...

  10. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Structure and Receptor Specificity of an Avian Flu Antigen Structure and Receptor Specificity of an Avian Flu Antigen Print Wednesday, 25 July 2007 00:00 To date, the H5N1 avian influenza viruses, which are currently circulating in domestic and wild birds on three continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of

  11. The forecast calls for flu

    Broader source: All U.S. Department of Energy (DOE) Office 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 ...

  12. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office 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 continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of genetic material from similar viruses) or mutation, is seen as a major threat to public

  13. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office 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 continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of genetic material from similar viruses) or mutation, is seen as a major threat to public

  14. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office 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 continents, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of genetic material from similar viruses) or mutation, is seen as a major threat to public

  15. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office 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, have only a limited ability to infect humans. However, with continued outbreaks of the virus in poultry and wild birds, the potential for the emergence of a human-adapted H5 virus, either by reassortment (the mixing of genetic material from similar viruses) or mutation, is seen as a major threat to public health

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

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    40 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

  17. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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 ...

  18. From biofuels to predicting the flu

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    From biofuels to predicting the flu From biofuels to predicting the flu WHEN: May 14, 2016 11:00 AM - 1:00 PM WHERE: Bradbury Science Museum 1350 Central Ave, Los Alamos, NM 87544, ...

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

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    The forecast calls for flu The forecast calls for flu Using mathematics, computer programs, statistics and information about how disease develops and spreads, a research team at Los Alamos National Laboratory found a way to forecast the flu season and even next week's sickness trends. January 15, 2016 Forecasting flu A team from Los Alamos has developed a method to predict flu outbreaks based in part on influenza-related searches of Wikipedia. The forecast calls for flu Beyond the familiar flu,

  20. Our view: Vaccinate now, prevent flu later

    Broader source: All U.S. Department of Energy (DOE) Office 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

  1. Picture of the Week: Forecasting Flu

    Broader source: All U.S. Department of Energy (DOE) Office 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

  2. Our view: Vaccinate now, prevent flu later

    Broader source: All U.S. Department of Energy (DOE) Office 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 ...

  3. Our view: Vaccinate now, prevent flu later

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  4. February most likely month for flu season to peak

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    February most likely month for flu season to peak February most likely month for flu season to peak The Los Alamos team's model is an ongoing research project that forecasts the current flu season probabilistically, similar to best-practice forecasts of weather, presidential elections, and sporting events. December 20, 2015 The Los Alamos team's model is an ongoing research project that forecasts the current flu season probabilistically, similar to best-practice forecasts of weather,

  5. Battling bird flu by the numbers

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Battling bird flu by the numbers Battling bird flu by the numbers Lab theorists have developed a mathematical tool that could help health experts and crisis managers determine in real time whether an emerging infectious disease such as avian influenza H5N1 is poised to spread globally. May 27, 2008 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,

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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 ...

  9. FLU5A425 | netl.doe.gov

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    FLU5A425 Methanogenesis in Hydrate-Bearing Sediments: Integration of Experimental and Theoretical Approaches FLU5A425/100400 Last Reviewed 01/22/2010 Project Goal To improve the understanding of processes that control the distribution, occurrence, and behavior of gas hydrate systems over time, especially with respect to the role played by these systems in global climate change. Performers Idaho National Laboratory, Idaho Falls, ID 83415 Oregon State University, Corvallis, OR 97331 Background The

  10. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  12. Microsoft Word - 1918flu.doc

    Broader source: All U.S. Department of Energy (DOE) Office 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

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  15. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  16. Science Summary

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    that can take out an unprecedented number of different types of flu viruses, including H5N1 'bird flu' and the 1918 H1N1 'Spanish flu', which killed millions around the world...

  17. Generating electricity from viruses

    SciTech Connect (OSTI)

    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.

  18. Generating electricity from viruses

    ScienceCinema (OSTI)

    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.

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

    Energy Savers [EERE]

    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 ...

  20. Production of virus resistant plants

    DOE Patents [OSTI]

    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.

  1. Production of virus resistant plants

    DOE Patents [OSTI]

    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.

  2. An introduction to computer viruses

    SciTech Connect (OSTI)

    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.

  3. From Shakespeare to Viruses

    ScienceCinema (OSTI)

    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.

  4. From Shakespeare to Viruses

    ScienceCinema (OSTI)

    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

  5. Computer virus information update CIAC-2301

    SciTech Connect (OSTI)

    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.

  6. Stanford Synchrotron Radiation Lightsource

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  7. 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...

  8. Recombinant herpes simplex virus useful for treating neoplastic disease

    DOE Patents [OSTI]

    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.

  9. 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 ...

  10. 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 ...

  11. 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 ...

  12. Presentation, Zika Virus Disease and Prevention | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Presentation, Zika Virus Disease and Prevention Presentation, Zika Virus Disease and Prevention May 19, 2016 Dr. Richter presented information about the rapid evolution of the Zika virus, the regions reporting active mosquito transmission of the Zika virus, the disease symptoms and preventative steps. Presentation, Zika Virus Disease and Prevention (678.7 KB) More Documents & Publications Worker Health Summary, 1995-2004 CAIRS Direct Data Entry (CDDE) Online Training Package FAQS Reference

  13. Zika Virus Disease and Prevention Presentation

    Broader source: 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.

  14. 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 ...

  15. Treatment of tumors with genetically engineered herpes virus

    DOE Patents [OSTI]

    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.

  16. Shutting Out Ebola and Other Viruses

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Shutting Out Ebola and Other Viruses Shutting Out Ebola and Other Viruses Print Thursday, 28 April 2016 00:00 Throughout the summer and fall of 2014, a tragic outbreak of Ebola hemorrhagic fever in West Africa reminded us of how interconnected the world is and how vulnerable we can be to the spread of virulent diseases. Science, however, gives us powerful tools for gaining insight into how pathogens operate and, consequently, how to design strategies to defeat them. Here we report on researchers

  17. Toward Design of a Universal Flu Vaccine

    Broader source: All U.S. Department of Energy (DOE) Office 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. ...

  18. Better predicting flu outbreaks with Wikipedia

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  19. Shutting Out Ebola and Other Viruses

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Shutting Out Ebola and Other Viruses Print Throughout the summer and fall of 2014, a tragic outbreak of Ebola hemorrhagic fever in West Africa reminded us of how interconnected the world is and how vulnerable we can be to the spread of virulent diseases. Science, however, gives us powerful tools for gaining insight into how pathogens operate and, consequently, how to design strategies to defeat them. Here we report on researchers from UC San Francisco who used protein crystallography at the ALS

  20. Shutting Out Ebola and Other Viruses

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Shutting Out Ebola and Other Viruses Print Throughout the summer and fall of 2014, a tragic outbreak of Ebola hemorrhagic fever in West Africa reminded us of how interconnected the world is and how vulnerable we can be to the spread of virulent diseases. Science, however, gives us powerful tools for gaining insight into how pathogens operate and, consequently, how to design strategies to defeat them. Here we report on researchers from UC San Francisco who used protein crystallography at the ALS

  1. Shutting Out Ebola and Other Viruses

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Shutting Out Ebola and Other Viruses Print Throughout the summer and fall of 2014, a tragic outbreak of Ebola hemorrhagic fever in West Africa reminded us of how interconnected the world is and how vulnerable we can be to the spread of virulent diseases. Science, however, gives us powerful tools for gaining insight into how pathogens operate and, consequently, how to design strategies to defeat them. Here we report on researchers from UC San Francisco who used protein crystallography at the ALS

  2. Shutting Out Ebola and Other Viruses

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Shutting Out Ebola and Other Viruses Print Throughout the summer and fall of 2014, a tragic outbreak of Ebola hemorrhagic fever in West Africa reminded us of how interconnected the world is and how vulnerable we can be to the spread of virulent diseases. Science, however, gives us powerful tools for gaining insight into how pathogens operate and, consequently, how to design strategies to defeat them. Here we report on researchers from UC San Francisco who used protein crystallography at the ALS

  3. Structure of the Triatoma virus capsid

    SciTech Connect (OSTI)

    Squires, Galle; Pous, Joan; Agirre, Jon; Rozas-Dennis, Gabriela S.; Costabel, Marcelo D.; Marti, Gerardo A.; Navaza, Jorge; Bressanelli, Stphane; Gurin, 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 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.

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

    Broader source: All U.S. Department of Energy (DOE) Office 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

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

    Broader source: All U.S. Department of Energy (DOE) Office 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. ...

  6. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office 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....

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

    Broader source: All U.S. Department of Energy (DOE) Office 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 apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if the cell doesn't die, it will spew all those new viruses into the bloodstream. The process of

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

    Broader source: All U.S. Department of Energy (DOE) Office 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 apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if the cell doesn't die, it will spew all those new viruses into the bloodstream. The process of

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

    Broader source: All U.S. Department of Energy (DOE) Office 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 apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if the cell doesn't die, it will spew all those new viruses into the bloodstream. The process of

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

    Broader source: All U.S. Department of Energy (DOE) Office 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 apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if the cell doesn't die, it will spew all those new viruses into the bloodstream. The process of

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

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Designer Proteins Target Epstein-Barr-Virus-Associated Cancer Print Wednesday, 03 December 2014 00:00 Immortality is not a good thing for cells, and in fact, cells will destroy themselves in a process called apoptosis when they are a danger to other cells. For instance, when a cell is infected by a virus it becomes an unwilling factory for the virus, which uses the cell machinery to produce ever more copies of itself. Eventually, if

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

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

    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 primersmore for West Nile Virus RNA detection. ...

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

    SciTech Connect (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.; 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.

  15. HIV virus spread and evolution studied through computer modeling

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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. ...

  18. 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...

  19. 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 (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  1. Risk of Zika virus is low in New Mexico

    Broader source: All U.S. Department of Energy (DOE) Office 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: September 1, 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

  2. Virus Assemblies as Templates for Nanocircuits

    SciTech Connect (OSTI)

    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.

  3. 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 ...

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

    Office of Scientific and Technical Information (OSTI)

    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 ...

  5. 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 ...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  7. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office 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....

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

    ScienceCinema (OSTI)

    Carolyn Bertozzi

    2010-01-08

    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.

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  10. High molecular weight polysaccharide that binds and inhibits virus

    DOE Patents [OSTI]

    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.

  11. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities Reveal Multiple Functions of Ebola Virus ALS Capabilities Reveal Multiple 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. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the

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

    SciTech Connect (OSTI)

    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.

  13. 1

    Broader source: All U.S. Department of Energy (DOE) Office 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

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

    SciTech Connect (OSTI)

    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.

  15. 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 ...

  16. Engineering Paper-Based Sensors for Zika Virus

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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.

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

    SciTech Connect (OSTI)

    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. Science Summary

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    H1N1 Flu » Links Scientific Highlight Wilson Lab Scripps Press Release Scripps Philanthrophy Science Magazine Vanderbilt Reporter » Share this Article Laboratree Ologeez SciLink LabSpaces Structural Basis for Senior Immunity to the Current H1N1 Flu summary written by Raven Hanna An unusual property of the last year's H1N1 "swine flu" virus pandemic is that it disproportionately affected the young. People over the age of around 65 showed much less vulnerability than to more typical

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

    SciTech Connect (OSTI)

    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.

  20. Virus-based Piezoelectric Energy Generation - Energy Innovation Portal

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Energy Storage Energy Storage Electricity Transmission Electricity Transmission Advanced Materials Advanced Materials Find More Like This Return to Search Virus-based Piezoelectric Energy Generation Lawrence Berkeley National Laboratory Contact LBL About This Technology Publications: PDF Document Publication Bacteriophage_Commercial Analysis_EERE_20130521 ps.pdf (1,100 KB) Technology Marketing Summary Researchers at Berkeley Lab have demonstrated that the piezoelectric and liquid-crystalline

  1. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities 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. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the protein. Recently, researchers used beamline capabilities at the ALS to demonstrate that a

  2. HIV virus spread and evolution studied through computer modeling

    Broader source: All U.S. Department of Energy (DOE) Office 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

  3. Molecular Insights into Crimean-Congo Hemorrhagic Fever Virus

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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.

  4. Structural Rearrangement in Ebola Virus Protein VP40 Creates Multiple

    Broader source: All U.S. Department of Energy (DOE) Office 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

  5. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities 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. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the protein. Recently, researchers used beamline capabilities at the ALS to demonstrate that a

  6. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities 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. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the protein. Recently, researchers used beamline capabilities at the ALS to demonstrate that a

  7. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    ALS Capabilities 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. Scientists typically expect that a protein has a singular structure (with some conformational variation), and that when an experimental structure is solved, it can used to understand the known biological function(s) of the protein. Recently, researchers used beamline capabilities at the ALS to demonstrate that a

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

    SciTech Connect (OSTI)

    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.

  9. Fast pandemic detection tool ready to fight flu

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    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...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  12. Structure and Receptor Specificity of an Avian Flu Antigen

    Broader source: All U.S. Department of Energy (DOE) Office 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. 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

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

    SciTech Connect (OSTI)

    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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  20. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein 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. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers from the Scripps Research

  1. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein 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. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers from the Scripps Research

  2. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein 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. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers from the Scripps Research

  3. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human Survivor Print Wednesday, 26 November 2008 00:00 Ebolavirus, one of two members of the family of filoviruses, causes a severe hemorrhagic fever with 50-90% human mortality. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of

  4. Structure of the Ebola Virus Glycoprotein Bound to an Antibody from a Human

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Survivor Structure of the Ebola Virus Glycoprotein 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. That no vaccines or treatments are yet available combined with the frequent re-emergence of the virus, its high prevalence among wildlife, and ease of importation of the virus make it a significant public health concern. A team of researchers from the Scripps Research

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  8. Improving Anti-Influenza Medications

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Anti-Influenza Medications Improving Anti-Influenza Medications Print Monday, 07 March 2016 16:16 The annual flu epidemics caused by influenza viruses, especially the influenza A virus, affect about 10-20% of the world's population each season. This highly contagious illness can trigger serious complications and can still lead at times to death, even today. Scientists have been working for a while with the M2 proton channel from the influenza A virus, which is one of nature's smallest

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

    SciTech Connect (OSTI)

    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.

  10. Virus and Bacterial Cell Chemical Analysis by NanoSIMS

    SciTech Connect (OSTI)

    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

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

    SciTech Connect (OSTI)

    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.

  12. News Item

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  13. NREL: Solar Research - News Release Archives

    Broader source: All U.S. Department of Energy (DOE) Office 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. ...

  14. 2012 News | Awards and Honors | NREL

    Broader source: All U.S. Department of Energy (DOE) Office 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 ...

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

    SciTech Connect (OSTI)

    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.

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

    DOE Patents [OSTI]

    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.

  17. Selective destruction of cells infected with human immunodeficiency virus

    DOE Patents [OSTI]

    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.

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

    SciTech Connect (OSTI)

    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.

  19. Crystal Structure of a Virus-Encoded Putative Glycosyltransferase

    SciTech Connect (OSTI)

    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}.

  20. Characterization of genetic variability of Venezuelan equine encephalitis viruses

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

  1. Alteration of cell cycle progression by Sindbis virus infection

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (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; 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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (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 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.

  7. 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 (OSTI)

    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.

  8. Three dimensional colorimetric assay assemblies

    DOE Patents [OSTI]

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    ScienceCinema (OSTI)

    Sullivan, Matthew B [University of Arizona

    2013-01-15

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (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; 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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (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; 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

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

    SciTech Connect (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 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

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (OSTI)

    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

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  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 (OSTI)

    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 Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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. Towards Breakthroughs in Protein Structure Calculation and Design | Argonne

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Leadership Computing Facility Hemagglutinin (orange) is an influenza surface protein responsible for viral invasion and infection of cells Hemagglutinin (orange) is an influenza surface protein responsible for viral invasion and infection of cells. Researchers in the Baker lab at the University of Washington have computationally designed a novel protein (blue) that binds to the base of hemagglutinin and effectively neutralizes the flu virus. Credit: Dr. Vikram K. Mulligan, University of

  18. SSRL HEADLINES March 2009

    Broader source: All U.S. Department of Energy (DOE) Office 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. Towards understanding of Nipah virus attachment protein assembly and the role of protein affinity and crowding for membrane curvature events.

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  2. 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 (OSTI)

    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

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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 (OSTI)

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (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 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.

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

    SciTech Connect (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 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.

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

    SciTech Connect (OSTI)

    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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  19. 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 (OSTI)

    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.

  20. 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 (OSTI)

    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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (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 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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  9. 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 (OSTI)

    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.

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

    SciTech Connect (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; 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.

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

    SciTech Connect (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.; 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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (OSTI)

    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.

  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 Supplemental Materials

    SciTech Connect (OSTI)

    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

  15. 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 (OSTI)

    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.

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (OSTI)

    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.

  19. 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 (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  1. 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 (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  4. NREL: Photovoltaics Research - News Release Archives

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2 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. December 4, 2012 NREL Teams with Berkeley Lab to Analyze Solar Pricing Trends and Benchmark "Soft" Costs for PV Systems The U.S. Department of Energy's (DOE)'s National Renewable Energy Laboratory (NREL) and Lawrence Berkeley National Laboratory (LBL) jointly released two reports examining solar photovoltaic (PV)

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  8. 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 (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  12. 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 (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  14. 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 (OSTI)

    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.

  15. 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 Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

  16. 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 (OSTI)

    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.

  17. Zika Virus Disease and Prevention

    Broader source: Energy.gov (indexed) [DOE]

    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 ...

  18. 2012 Feature Stories | NREL

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    2012 Feature Stories The following feature stories take an in-depth, behind-the-scenes look at how NREL is advancing energy efficiency and renewable energy technologies. December 2012 Award-Winning PV Cell Pushes Efficiency Higher 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. Award-Winning A/C Uses Old Idea, New Materials Award-Winning A/C Uses Old Idea, New Materials NREL's DEVAP cooling

  19. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    February most likely month for flu season to peak December 20, 2015 Los Alamos National Laboratory model predicts a late start to the flu season LOS ALAMOS, N.M., Dec. 15, 2015-The flu season will likely peak in February in most parts of the United States, according to a model developed by scientists at Los Alamos National Laboratory. Using historical data, a mathematical representation of how flu spreads through a population, and data for the current flu season provided by the Centers for

  20. 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 (OSTI)

    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

  1. Activated Carbon Injection

    ScienceCinema (OSTI)

    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.

  2. Activated Carbon Injection

    SciTech Connect (OSTI)

    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.

  3. ALSNews Vol. 338

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  4. ORISE: Process and Program Evaluation

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  5. 1663 March 2013

    Broader source: All U.S. Department of Energy (DOE) Office 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 ...

  6. 1

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  7. Smarter Drugs: How Protein Crystallography Revolutionizes Drug Design

    SciTech Connect (OSTI)

    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.

  8. Site Index - HPMC Occupational Health Services

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  10. Welcome to Stanford Synchrotron Radiation Lightsource | Stanford...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    SSRL Science in SLAC Today Q&A: Biologist Describes Milestone toward a Universal Flu Vaccine SSRL Upgrades, Adds Equipment for Next Round of Experiments X-ray Microscope Reveals...

  11. 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. ...

  12. 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 ...

  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. Human immunodeficiency virus type 1 clade M mosaic gag polypeptides

    DOE Patents [OSTI]

    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.

  15. This is a paper model of the MS2 virus

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Researchers hope that MS2 therapies will help them around this problem. One cause of diabetes is an auto-immune reaction in which a person's immune system attacks the islet cells...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    DOE Patents [OSTI]

    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.

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

    Broader source: All U.S. Department of Energy (DOE) Office 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...

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

    DOE Patents [OSTI]

    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.

  1. ALS Capabilities Reveal Multiple Functions of Ebola Virus

    Broader source: All U.S. Department of Energy (DOE) Office 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,...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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. ...

  3. 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. ...

  4. 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 (>

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

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

    SciTech Connect (OSTI)

    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.

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

    DOE Patents [OSTI]

    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.

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

    DOE Patents [OSTI]

    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.

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

    DOE Patents [OSTI]

    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.

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

    SciTech Connect (OSTI)

    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.

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

    SciTech Connect (OSTI)

    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.

  12. From Pandemic Preparedness to Biofuel Production: Tobacco Finds...

    Office of Scientific and Technical Information (OSTI)

    tobacco, has shown promise as an emergency intervention therapeutic against Ebola virus. ... upon genetic elements of tobacco mosaic virus (TMV) or other plant viruses that ...

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

    Broader source: All U.S. Department of Energy (DOE) Office 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. Discovery of Disease Co-occurrence Patterns from Electronic Healthcare Reimbursement Claims Data

    SciTech Connect (OSTI)

    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.

  15. SSRL HEADLINES April 2009

    Broader source: All U.S. Department of Energy (DOE) Office 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

  16. SSRL HEADLINES May 2010

    Broader source: All U.S. Department of Energy (DOE) Office 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

  17. News Item

    Broader source: All U.S. Department of Energy (DOE) Office 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

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

    SciTech Connect (OSTI)

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

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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. ...

  1. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    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 ...

  2. Metabolic characteristics of dominant microbes and key rare species...

    Office of Scientific and Technical Information (OSTI)

    ... Furthermore, based on CRISPR array analysis, there were also potential microbe-virus ... Since the order of spacers could be associated with time of virus infection, older spacers ...

  3. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

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

  4. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

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

  5. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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 ; ...

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

    Office of Scientific and Technical Information (OSTI)

    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 ...

  7. Search for: microbes OR Microbiomes | DOE PAGES

    Office of Scientific and Technical Information (OSTI)

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

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

    Office of Scientific and Technical Information (OSTI)

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

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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 ...

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

    Office of Scientific and Technical Information (OSTI)

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

  11. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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 ...

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

    Office of Scientific and Technical Information (OSTI)

    ... 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. ...

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

    Office of Scientific and Technical Information (OSTI)

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

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

    Office of Scientific and Technical Information (OSTI)

    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. ...

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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). ...

  16. Search for: All records | DOE PAGES

    Office of Scientific and Technical Information (OSTI)

    ... 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, ...

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

    Office of Scientific and Technical Information (OSTI)

    ... 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. ...

  18. Search for: All records | DOE PAGES

    Office of Scientific and Technical Information (OSTI)

    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 ...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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). ...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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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    Office of Scientific and Technical Information (OSTI)

    ... 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 ...

  2. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

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

  3. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

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

  4. 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 ...

  5. 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. ...

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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. ...

  7. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

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

  8. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    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 ...

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    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 ...

  10. 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 ...

  11. 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 ...

  12. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

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

  13. rep87-12.dvi

    Office of Scientific and Technical Information (OSTI)

    ... Hicks and C. L. Henley, "Irreversible growth model for virus capsid assembly", Phys. Rev. ... Cornell University (2010), "Statistical Mechanical Models Of Virus Capsid Assembly". ...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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 ...

  15. AFV CoverSheet

    Office of Scientific and Technical Information (OSTI)

    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 ...

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

    Office of Scientific and Technical Information (OSTI)

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

  17. Dr. Andrew Russo

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  18. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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. ...

  19. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... 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. ...

  20. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Anal Carcinoma in Human Immunodeficiency Virus-Positive Patients Receiving Highly Active ... anal carcinoma in human immunodeficiency virus (HIV)-infected patients receiving highly ...

  1. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    renormalization (3) trajectories (3) aids virus (2) basic biological sciences (2) lattice ... Immunogenic compositions comprising human immunodeficiency virus (HIV) mosaic Nef proteins ...

  2. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    nanotemplates of Tobacco mosaic virus using atomic layer deposition, exhibiting ... the patterning and templated synthesis of virus-structured nanomaterials in two- and ...

  3. Search for: All records | SciTech Connect

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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, ...

  4. Mathematical and Statistical Opportunities in Cyber Security

    Office of Scientific and Technical Information (OSTI)

    ... 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 ...

  5. Search for: All records | SciTech Connect

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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, ...

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... (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. ...

  7. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... NMR study of xenotropic murine leukemia virus-related virus protease in a complex with amprenavir Furukawa, Ayako ; Okamura, Hideyasu ; Morishita, Ryo ; Department of Microbiology, ...

  8. Search for: shape memory* | DOE PAGES

    Office of Scientific and Technical Information (OSTI)

    ... 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 ...

  9. 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 ...

  10. Analysis of the Argonne distance tabletop exercise method.

    SciTech Connect (OSTI)

    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

  11. Compound-specific effects of diverse neurodevelopmental toxicants on global gene expression in the neural embryonic stem cell test (ESTn)

    SciTech Connect (OSTI)

    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.

  12. Science on Tap - Forecasting illness

    Broader source: All U.S. Department of Energy (DOE) Office 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

  13. Hybrid fluidized bed combuster

    DOE Patents [OSTI]

    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.

  14. May Events

    Broader source: All U.S. Department of Energy (DOE) Office 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

  15. ORBiT: Oak Ridge Bio-surveillance Toolkit for Public Health Dynamics

    SciTech Connect (OSTI)

    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

  16. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Battling bird flu by the numbers May 27, 2008 Los Alamos mathematical model gauges epidemic potential of emerging diseases LOS ALAMOS, New Mexico, May 27, 2008-A pair of Los Alamos National Laboratory theorists have developed a mathematical tool that could help health experts and crisis managers determine in real time whether an emerging infectious disease such as avian influenza H5N1 is poised to spread globally. In a paper published recently in the Public Library of Science, researchers Luís

  17. HPMC Occupational Health Services

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Be Well Health Fair Play Featured Presentation September InsideOut WorkFit Training Flu Season - Save the Date Event Calendar Weight Loss Convoy Class--Third Quarter September 6, 2016 Convoy Alumni Meeting September 7, 2016 Site-Wide Health Fairs: BE WELL September 8, 2016 WorkFit Leader Training September 14, 2016 The BE WELL Challenge October 3, 2016 Weight Loss Convoy Maintenance Meeting October 4, 2016 News and Information August 29, 2016 BE WELL Get Shots to Protect Your Health August 29,

  18. ALSNews Vol. 278

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    8 Print Contents First proof of ferromagnetic carbon Symmetry breaking of H2 dissociation by a single photon Structure and receptor specificity of an avian flu antigen Material Management group keeps the ALS on track 2007 ALS Users' Meeting approaches News Links Engineers go history-free Breakthrough with ultra-fast x rays Chemically selective soft x-ray patterning of polymers Operations RING STATUS SCHEDULES For the user runs from June 26 - July 22: Beam reliability*: 90.6% Completion**: 83.7%

  19. ALSNews Vol. 278

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    8 ALSNews Vol. 278 Print Wednesday, 25 July 2007 00:00 Contents First proof of ferromagnetic carbon Symmetry breaking of H2 dissociation by a single photon Structure and receptor specificity of an avian flu antigen Material Management group keeps the ALS on track 2007 ALS Users' Meeting approaches News Links Engineers go history-free Breakthrough with ultra-fast x rays Chemically selective soft x-ray patterning of polymers Operations RING STATUS SCHEDULES For the user runs from June 26 - July

  20. ALSNews Vol. 278

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    8 Print Contents First proof of ferromagnetic carbon Symmetry breaking of H2 dissociation by a single photon Structure and receptor specificity of an avian flu antigen Material Management group keeps the ALS on track 2007 ALS Users' Meeting approaches News Links Engineers go history-free Breakthrough with ultra-fast x rays Chemically selective soft x-ray patterning of polymers Operations RING STATUS SCHEDULES For the user runs from June 26 - July 22: Beam reliability*: 90.6% Completion**: 83.7%

  1. 2011 - 09 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    09 Sep 2011 Tue, 2011-09-27 15:00 Performance Appraisal Process Begins 9/27/2011 Mon, 2011-09-26 15:00 Occ. Med. Offers Staff Flu Vaccines by Appointment Thu, 2011-09-15 15:00 JLab Adopts Event Policy to Avoid Scheduling Conflicts Tue, 2011-09-13 15:00 CS Parking Lot Closed During Test Lab Exterior Painting Thu, 2011-09-01 15:00 United Way Annual Appeal Underway at JLab Thu, 2011-09-01 15:00 Invitation to Celebrate JLab Founding Director's Contributions

  2. 2014 - 09 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office 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

  3. A role for granulocyte-macrophage colony-stimulating factor in the regulation of CD8{sup +} T cell responses to rabies virus

    SciTech Connect (OSTI)

    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.

  4. Cellular immune responses to HPV-18, -31, and -53 in healthy volunteers immunized with recombinant HPV-16 L1 virus-like particles

    SciTech Connect (OSTI)

    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. Quantitative autoradiography of muscarinic and benzodiazepine receptors in the forebrain of the turtle, Pseudemys scripta

    SciTech Connect (OSTI)

    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.

  6. 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 ...

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    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 ...

  8. 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 ...

  9. 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 ...

  10. 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. ...

  11. 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. ...

  12. 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 ...

  13. 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 ...

  14. 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 ...

  15. 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 ...

  16. 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 ...

  17. Search for: All records | SciTech Connect

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    ... 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 ...

  18. Search for: All records | SciTech Connect

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    ... 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. ...

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    ... 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 ...

  20. 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 --...

  1. 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 ...

  2. 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, ...

  3. 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, ...

  4. Microsoft Word - h1n1

    Broader source: All U.S. Department of Energy (DOE) Office 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 ...

  5. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  6. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  7. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office 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,...

  8. SN-03 Rate Hearing (7i) Files (ratecases/sn03)

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  9. 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 ...

  10. 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 ...

  11. 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 ...

  12. 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 ...

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    ... 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). ...

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    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 ...

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    ... 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. ...

  16. 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 ...

  17. Systems Biology in Prokaryote - Eukaryote Symbiosis | Stanford...

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Frontier challenges for macromolecular crystallography (MX) now include determining structures of trapped reactive intermediates, large macromolecules and viruses, membrane ...

  18. 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 (OSTI)

    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.

  19. 2012 - 09 | Jefferson Lab

    Broader source: All U.S. Department of Energy (DOE) Office 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

  20. 2015 - 09 | Jefferson Lab

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    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

  1. 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 (OSTI)

    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.

  2. Forecasting the 2013–2014 influenza season using Wikipedia

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

  3. Forecasting the 2013–2014 influenza season using Wikipedia

    SciTech Connect (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 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.

  4. Architecture for removable media USB-ARM

    SciTech Connect (OSTI)

    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.

  5. A bio-synthetic interface for discovery of viral entry mechanisms.

    SciTech Connect (OSTI)

    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.

  6. LOS ALAMOS, N.M., Nov. 19, 2013-Researchers at Los Alamos National Laboratory

    Broader source: All U.S. Department of Energy (DOE) Office 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

  7. Understanding the Key to Henipavirus Infection

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Understanding the Key to Henipavirus Infection Understanding the Key to Henipavirus Infection Print Wednesday, 15 June 2016 00:00 In 1994, a virus emerged in Hendra, Australia, causing respiratory and neurological diseases. It was transmissible from horses to humans, with a mortality rate of 57% in humans and 89% in horses. In 1999, a similar virus, transmitted through domesticated pigs, caused over 100 human deaths in Sungai Nipah, a Malaysian village. The Hendra and Nipah viruses are

  8. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office 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 refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure observations of the adsorption of carbon dioxide

  9. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office 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 refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure observations of the adsorption of carbon dioxide

  10. ALSNews Vol. 354

    Broader source: All U.S. Department of Energy (DOE) Office 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 refolding rearrangements to achieve three entirely different structures for three entirely separate functions in the virus life cycle. Read more... Contact: Erica Saphire An Inside Look at a MOF in Action mof Researchers have recorded the first in situ electronic-structure observations of the adsorption of carbon dioxide

  11. 1

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    deciphers HIV attack plan March 29, 2013 Scientists get inside look at how AIDS virus grooms its assault team LOS ALAMOS, N. M., March 29, 2013-A new study by Los Alamos National Laboratory and University of Pennsylvania scientists defines previously unknown properties of transmitted HIV-1, the virus that causes AIDS. The viruses that successfully pass from a chronically infected person to a new individual are both remarkably resistant to a powerful initial human immune-response mechanism, and

  12. 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 ...

  13. Nanomaterial Composites for Next Generation Water Filters: Cooperative Research and Development Final Report, CRADA Number CRD-06-197

    SciTech Connect (OSTI)

    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.

  14. 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...

  15. 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) ...

  16. 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 ...

  17. 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

  18. 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 ...

  19. SEQUEDEX

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    diseases (whether arising from bacteria, parasites, or viruses; characterizing gut, oral and skin microbiomes of humans, livestock, and pets; metagenomics of soils, rivers,...

  20. 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 ...

  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

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    June 15, 2010 2 West Nile Virus - Awareness * Hanford All Employee bulletins * Presidents' Zero Accident Council (PZAC) meeting attendance * AdvanceMed Hanford information links * ...

  3. CPL4001840-20151231100208

    Broader source: All U.S. Department of Energy (DOE) Office 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....

  4. EA-1363: Finding of No Significant Impact

    Broader source: 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

  5. Relationships between HIV spread and evolution examined

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    material of the virus. The researchers aim to utilize the HIV genetic footprint in mathematical models to reconstruct accurately how epidemics spread. The model systems could be...

  6. 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 ...

  7. The FELICIA bulletin board system and the IRBIS anonymous FTP server: Computer security information sources for the DOE community. CIAC-2302

    SciTech Connect (OSTI)

    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.

  8. 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 ; ...

  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. Using XAFS to Determine Origin of Ferromagnetism in LaCoO3 | Stanford

    Broader source: All U.S. Department of Energy (DOE) Office 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

  12. 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 ...

  13. 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. ; ...

  14. 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 ...

  15. 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 ...

  16. 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. ...

  17. 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. ...

  18. 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 ...

  19. 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. ...

  20. 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, ...

  1. 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 ...

  2. 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, ...

  3. "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...

  4. 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...

  5. 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...

  6. 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. ;...

  7. Work with Biological Materials

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  8. February | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    ... 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 ...

  9. 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...

  10. 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. ...

  11. Search for: microbes OR Microbiomes | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Targeted DNA extraction methods for bacteria, virus-like particles and induced prophages were used to generate bacterial and viral metagenomes as well as 16S ribosomal RNA ...

  12. 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 ; ...

  13. Science On Tap - Phylogenetics and Epidemics

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  14. LOS ALAMOS, N.M., Nov. 19, 2013-Researchers at Los Alamos National...

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  15. 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...

  16. 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. ...

  17. University of Medicine and Dentistry of New Jersey

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    rhinovirus);fungi ; vegetative bacteria; and, lipid or medium sized virus (herpes simplex, HIV, HBV). The table at the end of this section provides a framework for the...

  18. 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...

  19. 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) ...

  20. 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. ...

  1. Search for: All records | SciTech Connect

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    ... (2) quantum mechanics (2) qubits (2) transmission electron microscopy (2) aids virus (1) air pollution control (1) animal cells (1) anisotropy (1) antibodies (1) ...

  2. 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 ...

  3. Search for: All records | SciTech Connect

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    ... 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 ...

  4. 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 ...

  5. 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 ...

  6. 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. ...

  7. Search for: All records | SciTech Connect

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    Structure-Function Analysis of Vaccinia Virus H7 Protein Reveals a Novel Phosphoinositide Binding Fold Essential for Poxvirus Replication Kolli, Swapna ; Meng, Xiangzhi ; Wu, Xiang ...

  8. Search for: All records | SciTech Connect

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    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 ...

  9. Viral chemotherapy. Volume 2

    SciTech Connect (OSTI)

    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.

  10. Three-Dimensional Reconstruction of the Giant Mimivirus Particle with an X-Ray Free-Electron Laser

    DOE Data Explorer [Office of Scientific and Technical Information (OSTI)]

    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.

  11. TYLCV-Is movement in planta does not require V2 protein

    SciTech Connect (OSTI)

    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.

  12. Anti-influenza M2e antibody

    DOE Patents [OSTI]

    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.

  13. Anti-influenza M2e antibody

    DOE Patents [OSTI]

    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.

  14. Detection of bioagents using a shear horizontal surface acoustic wave biosensor

    DOE Patents [OSTI]

    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).

  15. Multiplex Degenerate Primer Design for Targeted Whole Genome Amplification of Many Viral Genomes

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

  16. Economic and policy implications of pandemic influenza.

    SciTech Connect (OSTI)

    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.

  17. I Am Science - and So Can You!

    SciTech Connect (OSTI)

    DiChristina, Mariette

    2013-05-08

    Science is humanitys 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 topicsthey just dont think of them as science. Consider how many of todays 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 toand a larger readership forscience-related materials than the world has ever known. Put another way, just when the public needs the Fourth Estate most, its instead drowning in a sea of 24/7 misinformation (a.k.a. the Internet). Whats a busy scientist to do to help engage the lay public? Glad you asked.

  18. Characterization of a novel insect-specific flavivirus from Brazil: Potential for inhibition of infection of arthropod cells with medically important flaviviruses.

    DOE Public Access Gateway for Energy & Science Beta (PAGES Beta)

    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

  19. DEFINING THE EFFECTIVENESS OF UV LAMPS

    Office of Scientific and Technical Information (OSTI)

    ... The infected cell may repair the damaged viral DNA for the virus if the infected cell contains the repair enzymes. 3.3.3 Recovery of Damaged Test Organisms The selection of the ...

  20. A Novel Secreted Protein, MYR1, Is Central to Toxoplasma's Manipulatio...

    Office of Scientific and Technical Information (OSTI)

    ... CC, Freedman ML, Blacklow SC, Aster JC, Bernstein BE, Kieff E. 2011. Epstein-Barr virus exploits intrinsic B-lymphocyte tran- scription programs to achieve immortal cell growth. ...

  1. 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 ...

  2. 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

  3. 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...

  4. Rf2a and rf2b transcription factors

    DOE Patents [OSTI]

    Beachy, Roger N.; Petruccelli, Silvana; Dai, Shunhong

    2007-10-02

    A method of activating the rice tungro bacilliform virus (RTBV) promoter in vivo is disclosed. The RTBV promoter is activated by exposure to at least one protein selected from the group consisting of Rf2a and Rf2b.

  5. 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 ...

  6. LA-8318-MS Informal Report I

    Office of Scientific and Technical Information (OSTI)

    ... D. (E-3) 2-75 QUANTITATION OF CELL FUSION BY TWENTY-ONE STRAINS OF NEWCASTLE DISEASE VIRUS USING FLOW MICROFLUOROMETRY. J. GEN. VIROL., V.41. P.27-36. 1978. CRAM, L. SCOTT (H-10) ...

  7. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... ; Zuo, Xiaobing ; Huffman, Jamie B. ; Homa, Fred L. ; Rau, Donald ; Evilevitch, Alex DNA in the human Herpes simplex virus type 1 (HSV-1) capsid is packaged to a tight density. ...

  8. rare_163_301.691_708.tp

    Office of Scientific and Technical Information (OSTI)

    ... These CArG promoters have been used suc- cessfully to drive expression of reporter (green fluorescent protein; GFP) and suicide gene (herpes simplex virus type 1 thymidine kinase...

  9. Search for: All records | DOE Patents

    Office of Scientific and Technical Information (OSTI)

    ... the cell walls or membrane of host cells one at a time so that a particular substance (e.g. a molecular tag, nucleic acid, bacteria, virus etc.) can be introduced into the cell. ...

  10. 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...

  11. EWA Summary.xls

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Guidance Software: Behshad Behnam ph: 703-657-7208 behshad.behnam@guidancesoftware.com DOE PM: Robert Ciochon ph: 202-586-2586 Robert.ciochon@hq.doe.gov IntelMcAfee Anti-virus and ...

  12. 'Let the phage do the work': Using the phage P22 coat protein structures as a framework to understand its folding and assembly mutants

    SciTech Connect (OSTI)

    Teschke, Carolyn M., E-mail: Teschke@uconn.ed [Departments of Molecular and Cell Biology, and Chemistry, 91 N. Eagleville Rd., U-3125, University of Connecticut, Storrs, CT 06269-3125 (United States); Parent, Kristin N. [Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA (United States)

    2010-06-05

    The amino acid sequence of viral capsid proteins contains information about their folding, structure and self-assembly processes. While some viruses assemble from small preformed oligomers of coat proteins, other viruses such as phage P22 and herpesvirus assemble from monomeric proteins (Fuller and King, 1980). The subunit assembly process is strictly controlled through protein:protein interactions such that icosahedral structures are formed with specific symmetries, rather than aberrant structures. dsDNA viruses commonly assemble by first forming a precursor capsid that serves as a DNA packaging machine. DNA packaging is accompanied by a conformational transition of the small precursor procapsid into a larger capsid for isometric viruses. Here we highlight the pseudo-atomic structures of phage P22 coat protein and rationalize several decades of data about P22 coat protein folding, assembly and maturation generated from a combination of genetics and biochemistry.

  13. Company/Product Description Contract Number Contract Holders

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    Lumension: Ben Boykin ph: 703-956-0347 ben.boykin@lumension.com Rob Gettings Robert.Gettings@hq.doe.gov 301-903-0829 McAfee Anti-virus and anti-spyware software (most McAfee ...

  14. Validating Computer-Designed Proteins for Vaccines

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    apply to a variety of other vaccine targets, such as human immunodeficiency virus and influenza. Wanted: Dead or Computed As strange as it sounds, most vaccines are composed of...

  15. Bette Korber, 2004 | U.S. DOE Office of Science (SC)

    Office of Science (SC) Website

    Print Text Size: A A A FeedbackShare Page Live Sciences: For her studies delineating the genetic characteristics of the HIV virus and for her development of the Los Alamos HIV ...

  16. University of Florida | OSTI, US Dept of Energy Office of Scientific...

    Office of Scientific and Technical Information (OSTI)

    grant to research pine-based biofuels New gene chip may help detect, treat West Nile virus in horses and humans UF teamed with USF, FSU and UCF to build the DOE Solar Decathlon ...

  17. C:\\Users\\28105\\Documents\\Choi ICF\\ESPA-LPT work\\RFI\\PDF Conversions...

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ... National Grid plc and its affiliates do not accept any liability for viruses. An e-mail reply to this address may be subject to monitoring for operational reasons or lawful ...

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

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    virus. The Sa site is located on the top of the HA trimer and colored in magenta. (B) Residual differences between CA04 and selected human H1 HAs in the Sa antigenic site ...

  19. Wavelength Comparison Radio Infrared Ultraviolet

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    ... What is the origin of the nuclei found on Earth? AM Radio Microwave Visible Sunlight X-ray TV and FM Radio Mt. Everest Skyscraper Person Pinhead Fingernail Virus Atom Atomic ...

  20. Apparatus and method for transforming living cells (Patent) ...

    Office of Scientific and Technical Information (OSTI)

    the cell walls or membrane of host cells one at a time so that a particular substance (e.g. a molecular tag, nucleic acid, bacteria, virus etc.) can be introduced into the cell. ...

  1. JC3 Bulletin Archive | Department of Energy

    Office of Energy Efficiency and Renewable Energy (EERE) Indexed Site

    A vulnerability was reported in McAfee VirusScan Enterprise. February 27, 2013 V-100: Adobe Flash Player Bugs Let Remote Users Execute Arbitrary Code Several vulnerabilities were...

  2. Validating Computer-Designed Proteins for Vaccines

    Broader source: All U.S. Department of Energy (DOE) Office 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...

  3. Environment/Health/Safety (EHS)

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    has been in the news. Measles is a highly contagious respiratory disease caused by a virus. It spreads through the air through coughing and sneezing. Measles can be spread days...

  4. "Human-on-a-Chip" Technology Could Replace Animal Testing | Department...

    Broader source: Energy.gov (indexed) [DOE]

    Maren Hunsberger takes us "Inside the Lab" to learn about the "human-on-a-chip" project. | ... viruses, or drugs on human beings without resorting to animal or even human test subjects? ...

  5. Consortium to design human trials of mosaic HIV vaccine

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Human trials of mosaic HIV vaccine Consortium to design human trials of mosaic HIV vaccine The vaccine represents a novel strategy for fighting the virus that causes AIDS by ...

  6. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    Everything44 Electronic Full Text0 Citations44 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject crystal structure (12) aids virus (7) design (7) synthesis (7) ...

  7. I

    Office of Scientific and Technical Information (OSTI)

    ... The LIC method relies on common linker sequences to anneal and join the target segments to the vector. A Tobacco Etch Virus (TEV) cleavage site allows cleavage of the fusion tag. ...

  8. University of Florida | OSTI, US Dept of Energy, Office of Scientific...

    Office of Scientific and Technical Information (OSTI)

    grant to research pine-based biofuels New gene chip may help detect, treat West Nile virus in horses and humans UF teamed with USF, FSU and UCF to build the DOE Solar Decathlon ...

  9. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Ribonucleic acid export 1 (Rae1) and Nup98 are evolutionarily conserved mRNA export factors that are targeted by the vesicular stomatitis virus matrix protein to inhibit host cell ...

  10. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... ; Bevilacqua, Philip C. ; Golden, Barbara L. ; Penn) The hepatitis delta virus (HDV) ribozyme and HDV-like ribozymes are self-cleaving RNAs found throughout all kingdoms of life. ...

  11. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Everything3 Electronic Full Text0 Citations3 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject aids virus (1) applied life sciences (1) basic biological sciences (1) ...

  12. Science and Technology Review December 2011 (Technical Report...

    Office of Scientific and Technical Information (OSTI)

    Track Viral Evolution - A sensitive technique developed at the Laboratory can identify virus mutations that may jump from host to host; and (5) Data for Defense: New Software Finds ...

  13. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Everything4 Electronic Full Text0 Citations4 Multimedia0 Datasets0 Software0 Filter Results Filter by Subject aids virus (1) applied life sciences (1) basic biological sciences (1) ...

  14. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Anna Marie ; NWU) We determined the size and shape of full-length avian sarcoma virus (ASV) integrase (IN) monomers and dimers in solution using small angle x-ray scattering. ...

  15. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Release from PD-1 inhibitory signaling revives 'exhausted' virus-specific T cells in chronic viral infections. Here we present the crystal structure of murine PD-1 in complex with ...

  16. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Innate immunity is our first line of defense against a pathogenic bacteria or virus. A comprehensive 'system-level' understanding of innate immunity pathways such as toll-like ...

  17. Search for: All records | SciTech Connect

    Office of Scientific and Technical Information (OSTI)

    ... Structure of a Dengue Virus Envelope Protein Late-Stage Fusion Intermediate Klein, Daryl E. ; Choi, Jason L. ; Harrison, Stephen C. ; CH-Boston) February 2013 Shape change in the ...

  18. Antibody evolution could guide HIV vaccine development

    Broader source: All U.S. Department of Energy (DOE) Office Webpages (Extended Search)

    Antibody evolution could guide HIV vaccine development Antibody evolution could guide HIV vaccine development The antibody studied is called a broadly cross-reactive neutralizing antibody, and details of its generation could provide a blueprint for effective vaccination. April 4, 2013 Co-evolution of virus and antibody - The evolution of the viral protein (green) from 14 weeks through 100 weeks post-transmission is compared to the maturation of the human antibody. Co-evolution of virus and

  19. T-612: False Positive Detection Generic.dx!yxk in DAT 6329

    Broader source: Energy.gov [DOE]

    This issue can affect all McAfee anti-virus products utilizing this DAT, however it will manifest itself only on endpoints such as VirusScan. Spsgui.exe - This file is typically found only on workstations that have the SAP client installed. This file is loaded by the SAP client when it starts up and is used to send and receive faxes inside the SAP application.

  20. Vaccine to control the viral infection of fish

    DOE Patents [OSTI]

    Leong, Jo-Ann C.

    1994-10-11

    Subunit vaccines and their use for immunizing fish against infection by viruses are disclosed. In particular, plasmid pG8 is constructed by joining, with the plasmid pUC8, DNA which encodes the glycoprotein of infectious hematopoietic necrosis virus (IHNV). E. coli cells are transformed by pG8, whereby pure viral antigen is produced to provide a vaccine for the control of IHNV in fish.