Characterization of a novel STAT 2 knock-out hamster model of Crimean-Congo hemorrhagic fever virus pathogenesis
Open Access
- 23 July 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-16
- https://doi.org/10.1038/s41598-020-69054-3
Abstract
Crimean-Congo hemorrhagic fever virus (CCHFV) is a tick-borne pathogen causing a febrile illness in humans, which can progress to hemorrhagic manifestations, multi-organ failure, and death. Current mouse models of CCHFV infection reliably succumb to virus challenge but vary in their ability to reflect signs of disease similar to humans. In this study, we established a signal transducer and activator of transcription 2 (STAT2) knockout hamster model to expand the repertoire of animal models of CCHFV pathogenesis that can be used for therapeutic development. These hamsters demonstrated a systemic and lethal disease in response to infection. Hallmarks of human disease were observed including petechial rash, blood coagulation dysfunction, and various biochemistry and blood cell count abnormalities. Furthermore, we also demonstrated the utility of this model for anti-CCHFV therapeutic evaluation. The STAT2 knock-out hamster model of CCHFV infection may provide some further insights into clinical disease, viral pathogenesis, and pave the way for testing of potential drug and vaccine candidates.Funding Information
- DIR, NIAID, NIH
- Public Heath Agency of Canada internal funding
This publication has 64 references indexed in Scilit:
- Animal Models of Tick-Borne Hemorrhagic Fever VirusesPathogens, 2013
- Cytokine and Chemokine Levels in Patients with Severe Fever with Thrombocytopenia Syndrome VirusPLOS ONE, 2012
- Crimean-‐Congo haemorrhagic fever: An outbreak in IndiaAustralasian Medical Journal, 2011
- Pathogenesis and Immune Response of Crimean-Congo Hemorrhagic Fever Virus in a STAT-1 Knockout Mouse ModelJournal of Virology, 2010
- Interacting Roles of Immune Mechanisms and Viral Load in the Pathogenesis of Crimean-Congo Hemorrhagic FeverClinical and Vaccine Immunology, 2010
- Pathogenic flavivirusesThe Lancet, 2008
- 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
- A new mathematical model for relative quantification in real-time RT-PCRNucleic Acids Research, 2001