Cargando…

Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever

BACKGROUND: Crimean Congo hemorrhagic fever (CCHF) is a tick-borne hemorrhagic zoonosis associated with high mortality. Pathogenesis studies and the development of vaccines and antivirals against CCHF have been severely hampered by the lack of suitable animal model. We recently developed and charact...

Descripción completa

Detalles Bibliográficos
Autores principales: Bowick, Gavin C, Airo, Adriana M, Bente, Dennis A
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2012
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489622/
https://www.ncbi.nlm.nih.gov/pubmed/22713837
http://dx.doi.org/10.1186/1743-422X-9-122
_version_ 1782248755586662400
author Bowick, Gavin C
Airo, Adriana M
Bente, Dennis A
author_facet Bowick, Gavin C
Airo, Adriana M
Bente, Dennis A
author_sort Bowick, Gavin C
collection PubMed
description BACKGROUND: Crimean Congo hemorrhagic fever (CCHF) is a tick-borne hemorrhagic zoonosis associated with high mortality. Pathogenesis studies and the development of vaccines and antivirals against CCHF have been severely hampered by the lack of suitable animal model. We recently developed and characterized a mature mouse model for CCHF using mice carrying STAT1 knockout (KO). FINDINGS: Given the importance of interferons in controlling viral infections, we investigated the expression of interferon pathway-associated genes in KO and wild-type (WT) mice challenged with CCHF virus. We expected that the absence of the STAT1 protein would result in minimal expression of IFN-related genes. Surprisingly, the KO mice showed high levels of IFN-stimulated gene expression, beginning on day 2 post-infection, while in WT mice challenged with virus the same genes were expressed at similar levels on day 1. CONCLUSIONS: We conclude that CCHF virus induces similar type I IFN responses in STAT1 KO and WT mice, but the delayed response in the KO mice permits rapid viral dissemination and fatal illness.
format Online
Article
Text
id pubmed-3489622
institution National Center for Biotechnology Information
language English
publishDate 2012
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-34896222012-11-06 Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever Bowick, Gavin C Airo, Adriana M Bente, Dennis A Virol J Short Report BACKGROUND: Crimean Congo hemorrhagic fever (CCHF) is a tick-borne hemorrhagic zoonosis associated with high mortality. Pathogenesis studies and the development of vaccines and antivirals against CCHF have been severely hampered by the lack of suitable animal model. We recently developed and characterized a mature mouse model for CCHF using mice carrying STAT1 knockout (KO). FINDINGS: Given the importance of interferons in controlling viral infections, we investigated the expression of interferon pathway-associated genes in KO and wild-type (WT) mice challenged with CCHF virus. We expected that the absence of the STAT1 protein would result in minimal expression of IFN-related genes. Surprisingly, the KO mice showed high levels of IFN-stimulated gene expression, beginning on day 2 post-infection, while in WT mice challenged with virus the same genes were expressed at similar levels on day 1. CONCLUSIONS: We conclude that CCHF virus induces similar type I IFN responses in STAT1 KO and WT mice, but the delayed response in the KO mice permits rapid viral dissemination and fatal illness. BioMed Central 2012-06-19 /pmc/articles/PMC3489622/ /pubmed/22713837 http://dx.doi.org/10.1186/1743-422X-9-122 Text en Copyright ©2012 Bowick et al.; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Short Report
Bowick, Gavin C
Airo, Adriana M
Bente, Dennis A
Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever
title Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever
title_full Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever
title_fullStr Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever
title_full_unstemmed Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever
title_short Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever
title_sort expression of interferon-induced antiviral genes is delayed in a stat1 knockout mouse model of crimean-congo hemorrhagic fever
topic Short Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3489622/
https://www.ncbi.nlm.nih.gov/pubmed/22713837
http://dx.doi.org/10.1186/1743-422X-9-122
work_keys_str_mv AT bowickgavinc expressionofinterferoninducedantiviralgenesisdelayedinastat1knockoutmousemodelofcrimeancongohemorrhagicfever
AT airoadrianam expressionofinterferoninducedantiviralgenesisdelayedinastat1knockoutmousemodelofcrimeancongohemorrhagicfever
AT bentedennisa expressionofinterferoninducedantiviralgenesisdelayedinastat1knockoutmousemodelofcrimeancongohemorrhagicfever