Lethal Crimean-Congo hemorrhagic fever virus infection in interferon α/β receptor knockout mice is associated with high viral loads, proinflammatory responses, and coagulopathy

Marko Zivcec, David Safronetz, Dana Scott, Shelly Robertson, Hideki Ebihara, Heinz Feldmann

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Crimean-Congo hemorrhagic fever (CCHF) is a widely distributed viral hemorrhagic fever characterized by rapid onset of flu-like symptoms often followed by hemorrhagic manifestations. CCHF virus (CCHFV), a bunyavirus in the Nairovirus genus, is capable of infecting a wide range of mammalian hosts in nature but so far only causes disease in humans. Recently, immunocompromised mice have been reported as CCHF disease models, but detailed characterization is lacking. Here, we closely followed infection and disease progression in CCHFV-infected interferon α/β receptor knockout (IFNAR-/-) mice and age-matched wild-type (WT) mice. WT mice quickly clear CCHFV without developing any disease signs. In contrast, CCHFV infected IFNAR-/- mice develop an acute fulminant disease with high viral loads leading to organ pathology (liver and lymphoid tissues), marked proinflammatory host responses, severe thrombocytopenia, coagulopathy, and death. Disease progression closely mimics hallmarks of human CCHF disease, making IFNAR-/- mice an excellent choice to assess medical countermeasures.

Original languageEnglish (US)
Pages (from-to)1909-1921
Number of pages13
JournalJournal of Infectious Diseases
Volume207
Issue number12
DOIs
StatePublished - Jun 15 2013

Keywords

  • CCHFV
  • coagulopathy
  • interferon α/β receptor knockout mice
  • pathology
  • proinflammatory response
  • thrombocytopenia

ASJC Scopus subject areas

  • Immunology and Allergy
  • Infectious Diseases

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