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

51 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Crimean-Congo hemorrhagic fever virus
Interferon Receptors
Virus Diseases
Viral Load
Knockout Mice
Crimean Hemorrhagic Fever
Congo
Viruses
Disease Progression
Nairovirus
Viral Hemorrhagic Fevers
Orthobunyavirus
Host Specificity
Lymphoid Tissue
Acute Disease
Thrombocytopenia
Pathology
Liver
Infection

Keywords

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

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Lethal Crimean-Congo hemorrhagic fever virus infection in interferon α/β receptor knockout mice is associated with high viral loads, proinflammatory responses, and coagulopathy. / Zivcec, Marko; Safronetz, David; Scott, Dana; Robertson, Shelly; Ebihara, Hideki; Feldmann, Heinz.

In: Journal of Infectious Diseases, Vol. 207, No. 12, 15.06.2013, p. 1909-1921.

Research output: Contribution to journalArticle

@article{25834cb3a3c746ffa35f6dfc2ace84a3,
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.",
keywords = "CCHFV, coagulopathy, interferon α/β receptor knockout mice, pathology, proinflammatory response, thrombocytopenia",
author = "Marko Zivcec and David Safronetz and Dana Scott and Shelly Robertson and Hideki Ebihara and Heinz Feldmann",
year = "2013",
month = "6",
day = "15",
doi = "10.1093/infdis/jit061",
language = "English (US)",
volume = "207",
pages = "1909--1921",
journal = "Journal of Infectious Diseases",
issn = "0022-1899",
publisher = "Oxford University Press",
number = "12",

}

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

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

UR - http://www.scopus.com/inward/record.url?scp=84877942060&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84877942060&partnerID=8YFLogxK

U2 - 10.1093/infdis/jit061

DO - 10.1093/infdis/jit061

M3 - Article

C2 - 23417661

AN - SCOPUS:84877942060

VL - 207

SP - 1909

EP - 1921

JO - Journal of Infectious Diseases

JF - Journal of Infectious Diseases

SN - 0022-1899

IS - 12

ER -