Simultaneous Detection of Ebola Virus and Pathogens Associated With Hemorrhagic Fever by an Oligonucleotide Microarray.
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ABSTRACT:
SUBMITTER: Yao W
PROVIDER: S-EPMC8363200 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Over the past 30 years, Zaire and Sudan ebolaviruses have been responsible for large hemorrhagic fever (HF) outbreaks with case fatalities ranging from 53% to 90%, while a third species, Côte d'Ivoire ebolavirus, caused a single non-fatal HF case. In November 2007, HF cases were reported in Bundibugyo District, Western Uganda. Laboratory investigation of the initial 29 suspect-case blood specimens by classic methods (antigen capture, IgM and IgG ELISA) and a recently developed random-primed pyrosequencing approach quickly identified this to be an Ebola HF outbreak associated with a newly discovered ebolavirus species (Bundibugyo ebolavirus) distantly related to the Côte d'Ivoire ebolavirus found in western Africa. Due to the sequence divergence of this new virus relative to all previously recognized ebolaviruses, these findings have important implications for design of future diagnostic assays to monitor Ebola HF disease in humans and animals, and ongoing efforts to develop effective antivirals and vaccines.
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Project description:Zaire ebolavirus (ZEBOV) is among the deadliest known human pathogens, causing severe hemorrhagic fever with high case fatality rates ranging from 70-90%. The lack of effective vaccines or treatment available for ZEBOV renders this pathogen as a significant global biodefense threat, as evidenced by the current, highly lethal outbreak of a novel ZEBOV variant in western Africa. Existing mouse models of lethal ZEBOV infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever (EHF) including prolonged blood coagulation, acute hepatitis, disseminated intravascular coagulation (DIC), and death from hemorrhagic shock, thus restricting pathogenesis studies to non-human primates (NHP). This has prevented rapid evaluation of countermeasures in outbreak scenarios, and impeded a comprehensive understanding of how host responses to infection contribute to severe EHF disease. Here we demonstrate that mice from the Collaborative Cross (CC), a panel of reproducible, recombinant inbred animals that span the genetic breadth of three murine subspecies, are susceptible to a spectrum of disease phenotypes following ZEBOV infection. In contrast to C57Bl6/J mice, which develop lethal disease without symptoms of EHF, CC recombinant inbred intercrossed (CC-RIX) lines develop either complete resistance to lethal disease or severe EHF characterized by prolonged coagulation times and 100% mortality. Disease resistance and survival is not dependent on viral tropism, as both resistant and EHF-susceptible lines show similar inflammation and cytopathic effect in target organs. Transcriptomics reveal potential mechanisms for both induction of severe hemorrhage in EHF mediated by IL-6 and vascular activation, and resistance to lethal infection by induction of lymphocyte differentiation and cellular adhesion. These data demonstrate that host responses specific to unique genetic backgrounds determine susceptibility to hemorrhagic syndrome independent of virus replication. The CC represents a novel mouse model for studying EHF pathogenesis, and we anticipate that it will be applied immediately to developing and evaluating therapeutic countermeasures. Microarrays were performed on liver and spleen samples from mice collected at days 1, 3, and 5 post-infection with mouse adapted Zaire ebolavirus or from time-matched mock-infected animals.
2014-05-01 | E-GEOD-57214 | biostudies-arrayexpress
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Project description:Zaire ebolavirus (ZEBOV) is among the deadliest known human pathogens, causing severe hemorrhagic fever with high case fatality rates ranging from 70-90%. The lack of effective vaccines or treatment available for ZEBOV renders this pathogen as a significant global biodefense threat, as evidenced by the current, highly lethal outbreak of a novel ZEBOV variant in western Africa. Existing mouse models of lethal ZEBOV infection do not reproduce hallmark symptoms of Ebola hemorrhagic fever (EHF) including prolonged blood coagulation, acute hepatitis, disseminated intravascular coagulation (DIC), and death from hemorrhagic shock, thus restricting pathogenesis studies to non-human primates (NHP). This has prevented rapid evaluation of countermeasures in outbreak scenarios, and impeded a comprehensive understanding of how host responses to infection contribute to severe EHF disease. Here we demonstrate that mice from the Collaborative Cross (CC), a panel of reproducible, recombinant inbred animals that span the genetic breadth of three murine subspecies, are susceptible to a spectrum of disease phenotypes following ZEBOV infection. In contrast to C57Bl6/J mice, which develop lethal disease without symptoms of EHF, CC recombinant inbred intercrossed (CC-RIX) lines develop either complete resistance to lethal disease or severe EHF characterized by prolonged coagulation times and 100% mortality. Disease resistance and survival is not dependent on viral tropism, as both resistant and EHF-susceptible lines show similar inflammation and cytopathic effect in target organs. Transcriptomics reveal potential mechanisms for both induction of severe hemorrhage in EHF mediated by IL-6 and vascular activation, and resistance to lethal infection by induction of lymphocyte differentiation and cellular adhesion. These data demonstrate that host responses specific to unique genetic backgrounds determine susceptibility to hemorrhagic syndrome independent of virus replication. The CC represents a novel mouse model for studying EHF pathogenesis, and we anticipate that it will be applied immediately to developing and evaluating therapeutic countermeasures.
2014-05-01 | GSE57214 | GEO
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