skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: Integrated sequence and immunology filovirus database at Los Alamos

Abstract

The Ebola outbreak of 2013–15 infected more than 28,000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. We report that as this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlightmore » the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.« less

Authors:
 [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1];  [1]
  1. Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Publication Date:
Research Org.:
Los Alamos National Lab. (LANL), Los Alamos, NM (United States)
Sponsoring Org.:
USDOE
OSTI Identifier:
1263542
Resource Type:
Journal Article: Accepted Manuscript
Journal Name:
Database
Additional Journal Information:
Journal Volume: 2016; Journal ID: ISSN 1758-0463
Publisher:
Oxford University Press
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES

Citation Formats

Yusim, Karina, Yoon, Hyejin, Foley, Brian, Feng, Shihai, Macke, Jennifer, Dimitrijevic, Mira, Abfalterer, Werner, Szinger, James, Fischer, Will, Kuiken, Carla, and Korber, Bette. Integrated sequence and immunology filovirus database at Los Alamos. United States: N. p., 2016. Web. doi:10.1093/database/baw047.
Yusim, Karina, Yoon, Hyejin, Foley, Brian, Feng, Shihai, Macke, Jennifer, Dimitrijevic, Mira, Abfalterer, Werner, Szinger, James, Fischer, Will, Kuiken, Carla, & Korber, Bette. Integrated sequence and immunology filovirus database at Los Alamos. United States. doi:10.1093/database/baw047.
Yusim, Karina, Yoon, Hyejin, Foley, Brian, Feng, Shihai, Macke, Jennifer, Dimitrijevic, Mira, Abfalterer, Werner, Szinger, James, Fischer, Will, Kuiken, Carla, and Korber, Bette. 2016. "Integrated sequence and immunology filovirus database at Los Alamos". United States. doi:10.1093/database/baw047. https://www.osti.gov/servlets/purl/1263542.
@article{osti_1263542,
title = {Integrated sequence and immunology filovirus database at Los Alamos},
author = {Yusim, Karina and Yoon, Hyejin and Foley, Brian and Feng, Shihai and Macke, Jennifer and Dimitrijevic, Mira and Abfalterer, Werner and Szinger, James and Fischer, Will and Kuiken, Carla and Korber, Bette},
abstractNote = {The Ebola outbreak of 2013–15 infected more than 28,000 people and claimed more lives than all previous filovirus outbreaks combined. Governmental agencies, clinical teams, and the world scientific community pulled together in a multifaceted response ranging from prevention and disease control, to evaluating vaccines and therapeutics in human trials. We report that as this epidemic is finally coming to a close, refocusing on long-term prevention strategies becomes paramount. Given the very real threat of future filovirus outbreaks, and the inherent uncertainty of the next outbreak virus and geographic location, it is prudent to consider the extent and implications of known natural diversity in advancing vaccines and therapeutic approaches. To facilitate such consideration, we have updated and enhanced the content of the filovirus portion of Los Alamos Hemorrhagic Fever Viruses Database. We have integrated and performed baseline analysis of all family Filoviridae sequences deposited into GenBank, with associated immune response data, and metadata, and we have added new computational tools with web-interfaces to assist users with analysis. Here, we (i) describe the main features of updated database, (ii) provide integrated views and some basic analyses summarizing evolutionary patterns as they relate to geo-temporal data captured in the database and (iii) highlight the most conserved regions in the proteome that may be useful for a T cell vaccine strategy.},
doi = {10.1093/database/baw047},
journal = {Database},
number = ,
volume = 2016,
place = {United States},
year = 2016,
month = 1
}

Journal Article:
Free Publicly Available Full Text
Publisher's Version of Record

Save / Share:
  • Ebola viruses and Marburg viruses, members of the filovirus family, are zoonotic pathogens that cause severe disease in people, as highlighted by the latest Ebola virus epidemic in West Africa. Filovirus disease is characterized by uncontrolled virus replication and the activation of host responses that contribute to pathogenesis. Underlying these phenomena is the potent suppression of host innate antiviral responses, particularly the type I interferon response, by viral proteins, which allows high levels of viral replication. In this Review, we describe the mechanisms used by filoviruses to block host innate immunity and discuss the links between immune evasion and filovirusmore » pathogenesis.« less
  • Epigraph is an efficient graph-based algorithm for designing vaccine antigens to optimize potential T-cell epitope (PTE) coverage. Functionally, epigraph vaccine antigens are similar to Mosaic vaccines, which have demonstrated effectiveness in preliminary HIV non-human primate studies. In contrast to the Mosaic algorithm, Epigraph is substantially faster, and in restricted cases, provides a mathematically optimal solution. Furthermore, epigraph has new features that enable enhanced vaccine design flexibility. These features include the ability to exclude rare epitopes from a design, to optimize population coverage based on inexact epitope matches, and to apply the code to both aligned and unaligned input sequences. Epigraphmore » was developed to provide practical design solutions for two outstanding vaccine problems. The first of these is a personalized approach to a therapeutic T-cell HIV vaccine that would provide antigens with an excellent match to an individual’s infecting strain, intended to contain or clear a chronic infection. The second is a pan-filovirus vaccine, with the potential to protect against all known viruses in the Filoviradae family, including ebolaviruses. A web-based interface to run the Epigraph tool suite is available (http://www.hiv.lanl.gov/content/sequence/EPIGRAPH/epigraph.html).« less
  • Research highlights: {yields} Filovirus glycoprotein (GP) having a deficient receptor binding region were generated. {yields} Mutant GPs mediated virus entry less efficiently than wild-type GP. {yields} Mutant GPs bound to C-type lectins but not mediated entire steps of cellular entry. {yields} C-type lectins do not independently mediate filovirus entry into cells. {yields} Other molecule(s) are required for C-type lectin-mediated entry of filoviruses. -- Abstract: Cellular C-type lectins have been reported to facilitate filovirus infection by binding to glycans on filovirus glycoprotein (GP). However, it is not clearly known whether interaction between C-type lectins and GP mediates all the steps ofmore » virus entry (i.e., attachment, internalization, and membrane fusion). In this study, we generated vesicular stomatitis viruses pseudotyped with mutant GPs that have impaired structures of the putative receptor binding regions and thus reduced ability to infect the monkey kidney cells that are routinely used for virus propagation. We found that infectivities of viruses with the mutant GPs dropped in C-type lectin-expressing cells, parallel with those in the monkey kidney cells, whereas binding activities of these GPs to the C-type lectins were not correlated with the reduced infectivities. These results suggest that C-type lectin-mediated entry of filoviruses requires other cellular molecule(s) that may be involved in virion internalization or membrane fusion.« less
  • Two new genes were identified and mapped by searching the EST databases with genomic sequences obtained from putative CpG islands of the rodent-human hybrid X3000. Previous mapping of these CpG islands in the proximity of the host cell factor (HCFC1) and GdX genes automatically localized these two new genes to Xq28 in the interval between the L1 cell adhesion molecule (L1CAM) and the glucose-6-phosphate dehydrogenase (G6PD) loci. Both genes are relatively short, contain an ORF of 261 and 105 amino acids, respectively, and are ubiquitously expressed. Combining sequencing of selected CpG islands, derived from hybrids containing small portions of themore » human genome, with an EST database search is an easy method of identifying and mapping new genes to specific regions of the genome. 17 refs., 4 figs.« less