The E2-E166K substitution restores Chikungunya virus growth in OAS3 expressing cells by acting on viral entry
Autor(es): Henrik Gad Hans, Paulous Sylvie, Belarbi Essia, Diancourt Laure, Drosten Christian, Kümmerer Beate M, Plate Aileen E, Caro Valérie, Desprès Philippe
Resumo: Human 2',5'-oligoadenylate synthetase 3 (OAS3) exerts antiviral effect against alphaviruses including Chikungunya virus (CHIKV) by inhibiting viral RNA accumulation. Here, we identified a CHIKV variant exhibiting a remarkable resistance to the antiviral action of OAS3 in human epithelial HeLa cells. Using a molecular clone of CHIKV with Renilla luciferase inserted as a reporter gene in the non-structural region, we demonstrated that a single glutamine-to-lysine amino acid change at position 166 of the envelope E2 glycoprotein restores CHIKV replication in OAS3 expressing HeLa cells. Viral entry assays showed that CHIKV with a lysine at position E2-166 was more efficient at entering the replicative pathway. The E2-E166K substitution promotes a greater efficiency of CHIKV replication in human myoblasts leading to severe apoptosis through a more robust activation of the PKR pathway. These observations provide a new insight into the role of E2 into the pathogenicity of CHIKV in human cells.
Palavras-Chave: Chikungunya virus; 2',5'-oligoadenylate synthetase; Innate immunity; Viral evasion; Myoblasts; Envelope glycoprotein; Molecular clone; Viral diversity
Imprenta: Virology, v. 434, n. 1, p. 27-37, 2012
Identificador do objeto digital: 10.1016/j.virol.2012.07.019
Descritores: Chikungunya virus - Biosynthesis ; Chikungunya virus - Cell ; Chikungunya virus - Genome ; Chikungunya virus - Pathogenesis ; Chikungunya virus - Protein synthesis ; Chikungunya virus - Proteins ; Chikungunya virus - RNA ; Chikungunya Virus - Virus ; Chikungunya virus - Immunology
Data de publicação: 2012
