Journal
JOURNAL OF INFECTIOUS DISEASES
Volume 207, Issue 12, Pages 1909-1921Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/infdis/jit061
Keywords
CCHFV; interferon alpha; beta receptor knockout mice; coagulopathy; thrombocytopenia; pathology; proinflammatory response
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Funding
- Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health
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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 alpha/beta 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.
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