Host response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model.


Journal

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

Informations de publication

Date de publication:
06 10 2021
Historique:
received: 03 05 2021
accepted: 14 09 2021
entrez: 7 10 2021
pubmed: 8 10 2021
medline: 28 12 2021
Statut: epublish

Résumé

Crimean-Congo hemorrhagic fever virus (CCHFV) is a highly pathogenic tick-borne RNA virus prevalent in Asia, Europe, and Africa, and can cause a hemorrhagic disease (CCHF) in humans with mortality rates as high as 60%. A general lack of both effective medical countermeasures and a comprehensive understanding of disease pathogenesis is partly driven by an historical lack of viable CCHF animal models. Recently, a cynomolgous macaque model of CCHF disease was developed. Here, we document the targeted transcriptomic response of non-human primates (NHP) to two different CCHFV strains; Afghan09-2990 and Kosova Hoti that both yielded a mild CCHF disease state. We utilized a targeted gene panel to elucidate the transcriptomic changes occurring in NHP whole blood during CCHFV infection; a first for any primate species. We show numerous upregulated genes starting at 1 day post-challenge through 14 days post-challenge. Early gene changes fell predominantly in the interferon stimulated gene family with later gene changes coinciding with an adaptive immune response to the virus. There are subtle differences between viral strains, namely duration of the differentially expressed gene response and biological pathways enriched. After recovery, NHPs showed no lasting transcriptomic changes at the end of sample collection.

Identifiants

pubmed: 34615921
doi: 10.1038/s41598-021-99130-1
pii: 10.1038/s41598-021-99130-1
pmc: PMC8494817
doi:

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

19807

Informations de copyright

© 2021. The Author(s).

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Auteurs

Catherine E Arnold (CE)

Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA. catherine.e.arnold13.civ@mail.mil.
Defense Threat Reduction Agency, Fort Belvoir, VA, USA. catherine.e.arnold13.civ@mail.mil.
Genomics and Bioinformatics Department, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, USA. catherine.e.arnold13.civ@mail.mil.

Charles J Shoemaker (CJ)

Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

Darci R Smith (DR)

Virology Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
Immunodiagnostics Department, Biological Defense Research Directorate, Naval Medical Research Center, Fort Detrick, MD, USA.

Christina E Douglas (CE)

Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

Candace D Blancett (CD)

Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.

Amanda S Graham (AS)

Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA.
National Biodefense Analysis and Countermeasures Center, Fort Detrick, MD, USA.

Timothy D Minogue (TD)

Diagnostic Systems Division, U.S. Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD, USA. timothy.d.minogue.civ@mail.mil.

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