Viral determinants in the NS3 helicase and 2K peptide that promote West Nile virus resistance to antiviral action of 2′,5′-oligoadenylate synthetase 1b

Mertens, E, Kajaste-Rudnitski, A, Torres, S, Funk, A, Frenkiel, MP, Iteman, I, Khromykh, AA and Despres, P (2010) Viral determinants in the NS3 helicase and 2K peptide that promote West Nile virus resistance to antiviral action of 2′,5′-oligoadenylate synthetase 1b. Virology, 399 1: 176-185. doi:10.1016/j.virol.2009.12.036


Author Mertens, E
Kajaste-Rudnitski, A
Torres, S
Funk, A
Frenkiel, MP
Iteman, I
Khromykh, AA
Despres, P
Title Viral determinants in the NS3 helicase and 2K peptide that promote West Nile virus resistance to antiviral action of 2′,5′-oligoadenylate synthetase 1b
Journal name Virology   Check publisher's open access policy
ISSN 0042-6822
1089-862X
1096-0341
Publication date 2010-03-30
Sub-type Article (original research)
DOI 10.1016/j.virol.2009.12.036
Volume 399
Issue 1
Start page 176
End page 185
Total pages 10
Place of publication Maryland Heights, MO, U.S.A.
Publisher Academic Press
Collection year 2011
Language eng
Abstract The interferon-inducible 2′,5′-oligoadenylate synthetase 1b (Oas1b) protein inhibits West Nile virus (WNV) infection by preventing viral RNA (vRNA) accumulation in infected cells. Serial passage of WNV in Oas1b-expressing mouse cells selected a virus variant with improved growth capacity. Two major amino acid substitutions were identified in this Oas1b-resistant WNV variant: NS3-S365G in the ATPase/helicase domain of NS3 and 2K-V9M in the C-terminal segment of NS4A. To assess their effect on antiviral activity of Oas1b, the NS3 and 2K mutations were engineered into an infectious WNV cDNA clone. The NS3 mutation alters requirement of ATP for ATPase activity and attenuates Oas1b-mediated suppression of vRNA accumulation. However, growth of NS3-mutant virus remains impaired in Oas1b-expressing cells. Only the 2K-V9M mutation efficiently rescued viral growth by promoting vRNA replication. Thus, WNV resistance to Oas1b antiviral action could be attributed to the 2K-V9M substitution with a potential role of NS3-S365G through rescue of vRNA accumulation. © 2009 Elsevier Inc. All rights reserved.
Keyword West Nile virus
2 ',5 '-oligoadenylate synthetases
Innate immunity
Viral evasion
Flavivirus 2K peptide
Flavivirus NS3 helicase
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2011 Collection
School of Chemistry and Molecular Biosciences
 
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Created: Sun, 28 Mar 2010, 00:01:11 EST