Molecular determinants of Ebola virus virulence in mice

Hideki Ebihara, Ayato Takada, Darwyn Kobasa, Steven Jones, Gabriele Neumann, Steven Theriault, Mike Bray, Heinz Feldmann, Yoshihiro Kawaoka

Research output: Contribution to journalArticle

152 Scopus citations

Abstract

Zaire ebolavirus (ZEBOV) causes severe hemorrhagic fever in humans and nonhuman primates, with fatality rates in humans of up to 90%. The molecular basis for the extreme virulence of ZEBOV remains elusive. While adult mice resist ZEBOV infection, the Mayinga strain of the virus has been adapted to cause lethal infection in these animals. To understand the pathogenesis underlying the extreme virulence of Ebola virus (EBOV), here we identified the mutations responsible for the acquisition of the high virulence of the adapted Mayinga strain in mice, by using reverse genetics. We found that mutations in viral protein 24 and in the nucleoprotein were primarily responsible for the acquisition of high virulence. Moreover, the role of these proteins in virulence correlated with their ability to evade type I interferon-stimulated antiviral responses. These findings suggest a critical role for overcoming the interferon-induced antiviral state in the pathogenicity of EBOV and offer new insights into the pathogenesis of EBOV infection.

Original languageEnglish (US)
Pages (from-to)705-711
Number of pages7
JournalPLoS pathogens
Volume2
Issue number7
DOIs
StatePublished - Aug 4 2006

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Ebihara, H., Takada, A., Kobasa, D., Jones, S., Neumann, G., Theriault, S., Bray, M., Feldmann, H., & Kawaoka, Y. (2006). Molecular determinants of Ebola virus virulence in mice. PLoS pathogens, 2(7), 705-711. https://doi.org/10.1371/journal.ppat.0020073