title: Lethal Crimean-Congo hemorrhagic fever virus infection in interferon α/β receptor knockout mice is associated with high viral loads, proinflammatory responses, and coagulopathy.
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.
authors: Laboratory of Virology, Division of Intramural Research, National Institute Allergy and Infectious Disease, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, Montana, USA.
authors: Marko
authors: M
authors: Zivcec
authors: David
authors: D
authors: Safronetz
authors: Dana
authors: D
authors: Scott
authors: Shelly
authors: S
authors: Robertson
authors: Hideki
authors: H
authors: Ebihara
authors: Heinz
authors: H
authors: Feldmann
mesh_terms: D000818:Animals; D001778:Blood Coagulation Disorders / Q000276:immunology / Q000473:pathology / Q000821:virology; D018925:Chemokines / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D018450:Disease Progression; D003225:Hemorrhagic Fever Virus, Crimean-Congo / Q000276:immunology* / Q000502:physiology; D006479:Hemorrhagic Fever, Crimean / Q000150:complications / Q000276:immunology* / Q000473:pathology; D006801:Humans; D008099:Liver / Q000473:pathology / Q000821:virology; D017114:Liver Failure, Acute / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008221:Lymphoid Tissue / Q000473:pathology / Q000821:virology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D053633:Receptor, Interferon alpha-beta / Q000235:genetics* / Q000276:immunology; D013154:Spleen / Q000473:pathology / Q000821:virology; D013921:Thrombocytopenia / Q000276:immunology / Q000473:pathology / Q000821:virology; D019562:Viral Load; D014766:Viremia
chemical_list: D018925:Chemokines; D016207:Cytokines; D053633:Receptor, Interferon alpha-beta
keywords: CCHFV; coagulopathy; interferon α/β receptor knockout mice; pathology; proinflammatory response; thrombocytopenia