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
Eva MertensPhilippe Desprès

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.

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Citations

Dec 5, 2013·Viruses·Siew Pheng Lim, Pei-Yong Shi
Jul 22, 2014·Viruses·Willy W SuenHelle Bielefeldt-Ohmann
Mar 24, 2012·Expert Opinion on Drug Discovery·Carolyn Botting, Richard J Kuhn
Jul 30, 2014·Virus Research·Samantha BuruguAnne Gatignol
Jan 10, 2012·Infection, Genetics and Evolution : Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases·Kendra N Pesko, Gregory D Ebel
Apr 12, 2012·World Journal of Virology·Miguel A Martín-Acebes, Juan-Carlos Saiz
Dec 29, 2010·Veterinary Research·Kristy O MurrayPhilippe Despres
Jul 19, 2021·European Journal of Medicinal Chemistry·Igor José Dos Santos NascimentoEdeildo Ferreira da Silva-Júnior

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