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.
| Original language | English |
|---|---|
| Pages (from-to) | 176-185 |
| Number of pages | 10 |
| Journal | Virology |
| Volume | 399 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Mar 30 2010 |
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Keywords
- 2′,5′-oligoadenylate synthetases
- Flavivirus 2K peptide
- Flavivirus NS3 helicase
- Innate immunity
- Viral evasion
- West Nile virus
ASJC Scopus subject areas
- Virology
Cite this
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, Eva; Kajaste-Rudnitski, Anna; Torres, Shessy; Funk, Anneke; Frenkiel, Marie Pascale; Iteman, Isabelle; Khromykh, Alexander A.; Desprès, Philippe.
In: Virology, Vol. 399, No. 1, 30.03.2010, p. 176-185.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Viral determinants in the NS3 helicase and 2K peptide that promote West Nile virus resistance to antiviral action of 2′,5′-oligoadenylate synthetase 1b
AU - Mertens, Eva
AU - Kajaste-Rudnitski, Anna
AU - Torres, Shessy
AU - Funk, Anneke
AU - Frenkiel, Marie Pascale
AU - Iteman, Isabelle
AU - Khromykh, Alexander A.
AU - Desprès, Philippe
PY - 2010/3/30
Y1 - 2010/3/30
N2 - 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.
AB - 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.
KW - 2′,5′-oligoadenylate synthetases
KW - Flavivirus 2K peptide
KW - Flavivirus NS3 helicase
KW - Innate immunity
KW - Viral evasion
KW - West Nile virus
UR - http://www.scopus.com/inward/record.url?scp=77249129709&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=77249129709&partnerID=8YFLogxK
U2 - 10.1016/j.virol.2009.12.036
DO - 10.1016/j.virol.2009.12.036
M3 - Article
C2 - 20100623
AN - SCOPUS:77249129709
VL - 399
SP - 176
EP - 185
JO - Virology
JF - Virology
SN - 0042-6822
IS - 1
ER -