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

Abstract 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 comprehen...

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Autores principales:	Catherine E. Arnold, Charles J. Shoemaker, Darci R. Smith, Christina E. Douglas, Candace D. Blancett, Amanda S. Graham, Timothy D. Minogue
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c8efa106ddde4386af922402d4e950f1
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spelling	oai:doaj.org-article:c8efa106ddde4386af922402d4e950f12021-12-02T18:07:52ZHost response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model10.1038/s41598-021-99130-12045-2322https://doaj.org/article/c8efa106ddde4386af922402d4e950f12021-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-99130-1https://doaj.org/toc/2045-2322Abstract 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.Catherine E. ArnoldCharles J. ShoemakerDarci R. SmithChristina E. DouglasCandace D. BlancettAmanda S. GrahamTimothy D. MinogueNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-9 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Catherine E. Arnold Charles J. Shoemaker Darci R. Smith Christina E. Douglas Candace D. Blancett Amanda S. Graham Timothy D. Minogue Host response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model
description	Abstract 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.
format	article
author	Catherine E. Arnold Charles J. Shoemaker Darci R. Smith Christina E. Douglas Candace D. Blancett Amanda S. Graham Timothy D. Minogue
author_facet	Catherine E. Arnold Charles J. Shoemaker Darci R. Smith Christina E. Douglas Candace D. Blancett Amanda S. Graham Timothy D. Minogue
author_sort	Catherine E. Arnold
title	Host response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model
title_short	Host response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model
title_full	Host response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model
title_fullStr	Host response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model
title_full_unstemmed	Host response transcriptomic analysis of Crimean-Congo hemorrhagic fever pathogenesis in the cynomolgus macaque model
title_sort	host response transcriptomic analysis of crimean-congo hemorrhagic fever pathogenesis in the cynomolgus macaque model
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/c8efa106ddde4386af922402d4e950f1
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_version_	1718378656901890048

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

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