Lethal Crimean-Congo Hemorrhagic Fever Virus Infection in Interferon α/β Receptor Knockout Mice Is Associated With High Viral Loads, Proinflammatory Responses, and Coagulopathy
Open Access
- 15 February 2013
- journal article
- research article
- Published by Oxford University Press (OUP) in The Journal of Infectious Diseases
- Vol. 207 (12), 1909-1921
- https://doi.org/10.1093/infdis/jit061
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
This publication has 44 references indexed in Scilit:
- Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse ModelJournal of Virology, 2010
- Crimean-Congo hemorrhagic fever in childrenJournal of Clinical Virology, 2010
- Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic FeverClinical and Vaccine Immunology, 2010
- Coagulopathy parameters in patients with Crimean-Congo hemorrhagic fever and its relation with mortalityJournal of Clinical Laboratory Analysis, 2010
- Crimean-Congo hemorrhagic fever virus infection is lethal for adult type I interferon receptor-knockout miceJournal of General Virology, 2010
- Ovarian Tumor Domain-Containing Viral Proteases Evade Ubiquitin- and ISG15-Dependent Innate Immune ResponsesCell Host & Microbe, 2007
- Viral Load as Predictor of Crimean-Congo Hemorrhagic Fever OutcomeEmerging Infectious Diseases, 2007
- Virus Detection and Monitoring of Viral Load in Crimean-Congo Hemorrhagic Fever Virus PatientsEmerging Infectious Diseases, 2007
- Viral Load and Crimean-Congo Hemorrhagic FeverEmerging Infectious Diseases, 2007
- Crimean–Congo hemorrhagic feverAntiviral Research, 2004