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

Gavin C. Bowick, Adriana M. Airo, Dennis Bente

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number122
JournalVirology Journal
Volume9
DOIs
StatePublished - 2012

Fingerprint

Crimean Hemorrhagic Fever
Congo
Knockout Mice
Interferons
Antiviral Agents
Crimean-Congo hemorrhagic fever virus
Genes
STAT1 Transcription Factor
Gene Knockout Techniques
Zoonoses
Ticks
Virus Diseases
Vaccines
Animal Models
Viruses
Gene Expression
Mortality
Infection

Keywords

  • Animal model
  • Crimean Congo hemorrhagic fever
  • Interferon
  • Signaling
  • STAT1

ASJC Scopus subject areas

  • Virology
  • Infectious Diseases

Cite this

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.

In: Virology Journal, Vol. 9, 122, 2012.

Research output: Contribution to journalArticle

@article{525e95079cc540e8aa56a7e3894c95cd,
title = "Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever",
abstract = "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.",
keywords = "Animal model, Crimean Congo hemorrhagic fever, Interferon, Signaling, STAT1",
author = "Bowick, {Gavin C.} and Airo, {Adriana M.} and Dennis Bente",
year = "2012",
doi = "10.1186/1743-422X-9-122",
language = "English (US)",
volume = "9",
journal = "Virology Journal",
issn = "1743-422X",
publisher = "BioMed Central",

}

TY - JOUR

T1 - Expression of interferon-induced antiviral genes is delayed in a STAT1 knockout mouse model of Crimean-Congo hemorrhagic fever

AU - Bowick, Gavin C.

AU - Airo, Adriana M.

AU - Bente, Dennis

PY - 2012

Y1 - 2012

N2 - 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.

AB - 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.

KW - Animal model

KW - Crimean Congo hemorrhagic fever

KW - Interferon

KW - Signaling

KW - STAT1

UR - http://www.scopus.com/inward/record.url?scp=84862289065&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84862289065&partnerID=8YFLogxK

U2 - 10.1186/1743-422X-9-122

DO - 10.1186/1743-422X-9-122

M3 - Article

VL - 9

JO - Virology Journal

JF - Virology Journal

SN - 1743-422X

M1 - 122

ER -