Characterization of a novel STAT 2 knock-out hamster model of Crimean-Congo hemorrhagic fever virus pathogenesis.


Journal

Scientific reports
ISSN: 2045-2322
Titre abrégé: Sci Rep
Pays: England
ID NLM: 101563288

Informations de publication

Date de publication:
23 07 2020
Historique:
received: 12 05 2020
accepted: 30 06 2020
entrez: 25 7 2020
pubmed: 25 7 2020
medline: 15 12 2020
Statut: epublish

Résumé

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.

Identifiants

pubmed: 32704046
doi: 10.1038/s41598-020-69054-3
pii: 10.1038/s41598-020-69054-3
pmc: PMC7378551
doi:

Substances chimiques

STAT2 Transcription Factor 0

Types de publication

Journal Article Research Support, N.I.H., Intramural Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

12378

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Auteurs

Charlene Ranadheera (C)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, Canada.
Bioforensics Assay Development and Diagnostics, National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, MB, Canada.

Emelissa J Valcourt (EJ)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, Canada.

Bryce M Warner (BM)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, Canada.
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.

Guillaume Poliquin (G)

Office of the Scientific Director, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, Canada.
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada.

Kyle Rosenke (K)

Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.

Kathy Frost (K)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, Canada.

Kevin Tierney (K)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, Canada.

Greg Saturday (G)

Rocky Mountain Veterinary Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.

Jinxin Miao (J)

Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.
Department of Pathology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, 450066, People's Republic of China.

Jonna B Westover (JB)

Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.

Brian B Gowen (BB)

Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.

Stephanie Booth (S)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, Canada.
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada.

Heinz Feldmann (H)

Laboratory of Virology, Division of Intramural Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rocky Mountain Laboratories, Hamilton, MT, USA.

Zhongde Wang (Z)

Department of Animal, Dairy, and Veterinary Sciences, Utah State University, Logan, UT, USA.

David Safronetz (D)

Zoonotic Diseases and Special Pathogens, National Microbiology Laboratories, Public Health Agency of Canada, Winnipeg, MB, Canada. david.safronetz@canada.ca.
Department of Medical Microbiology, University of Manitoba, Winnipeg, MB, Canada. david.safronetz@canada.ca.

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Classifications MeSH