West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type I interferon-mediated antiviral response

Schuessler, Andrea, Funk, Anneke, Lazear, Helen M., Cooper, Daphne A., Torres, Shessy, Daffis, Stephane, Jha, Babal Kant, Kumagai, Yutaro, Takeuchi, Osamu, Hertzog, Paul, Silverman, Robert, Akira, Shizuo, Barton, David J., Diamond, Michael S. and Khromykh, Alexander A. (2012) West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type I interferon-mediated antiviral response. Journal of Virology, 86 10: 5708-5718.


Author Schuessler, Andrea
Funk, Anneke
Lazear, Helen M.
Cooper, Daphne A.
Torres, Shessy
Daffis, Stephane
Jha, Babal Kant
Kumagai, Yutaro
Takeuchi, Osamu
Hertzog, Paul
Silverman, Robert
Akira, Shizuo
Barton, David J.
Diamond, Michael S.
Khromykh, Alexander A.
Title West Nile virus noncoding subgenomic RNA contributes to viral evasion of the type I interferon-mediated antiviral response
Journal name Journal of Virology   Check publisher's open access policy
ISSN 0022-538X
1098-5514
Publication date 2012-05
Sub-type Article (original research)
DOI 10.1128/JVI.00207-12
Volume 86
Issue 10
Start page 5708
End page 5718
Total pages 11
Place of publication Washington, DC, United States
Publisher American Society for Microbiology
Collection year 2013
Language eng
Abstract We previously showed that a noncoding subgenomic flavivirus RNA (sfRNA) is required for viral pathogenicity, as a mutant West Nile virus (WNV) deficient in sfRNA production replicated poorly in wild-type mice. To investigate the possible immunomodulatory or immune evasive functions of sfRNA, we utilized mice and cells deficient in elements of the type I interferon (IFN) response. Replication of the sfRNA mutant WNV was rescued in mice and cells lacking interferon regulatory factor 3 (IRF-3) and IRF-7 and in mice lacking the type I alpha/beta interferon receptor (IFNAR), suggesting a contribution for sfRNA in overcoming the antiviral response mediated by type I IFN. This was confirmed by demonstrating rescue of mutant virus replication in the presence of IFNAR neutralizing antibodies, greater sensitivity of mutant virus replication to IFN-α pretreatment, partial rescue of its infectivity in cells deficient in RNase L, and direct effects of transfected sfRNA on rescuing replication of unrelated Semliki Forest virus in cells pretreated with IFN-α. The results define a novel function of sfRNA in flavivirus pathogenesis via its contribution to viral evasion of the type I interferon response.
Keyword Kunjin Virus
Alpha/beta-Interferon
Japanese Encephalitis
Regulatory Factor-3
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Published online ahead of print on 29 February 2012.

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2013 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Tue, 01 May 2012, 14:15:56 EST by Andrea Schuessler on behalf of School of Chemistry & Molecular Biosciences