TY - JOUR
T1 - Lethal Crimean-Congo hemorrhagic fever virus infection in interferon α/β receptor knockout mice is associated with high viral loads, proinflammatory responses, and coagulopathy
AU - Zivcec, Marko
AU - Safronetz, David
AU - Scott, Dana
AU - Robertson, Shelly
AU - Ebihara, Hideki
AU - Feldmann, Heinz
N1 - Funding Information:
Financial support. This work was supported by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health. Potential conflict of interest. All authors: No reported conflicts.
PY - 2013/6/15
Y1 - 2013/6/15
N2 - 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.
AB - 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.
KW - CCHFV
KW - coagulopathy
KW - interferon α/β receptor knockout mice
KW - pathology
KW - proinflammatory response
KW - thrombocytopenia
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U2 - 10.1093/infdis/jit061
DO - 10.1093/infdis/jit061
M3 - Article
C2 - 23417661
AN - SCOPUS:84877942060
SN - 0022-1899
VL - 207
SP - 1909
EP - 1921
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 12
ER -