The E2-E166K substitution restores Chikungunya virus growth in OAS3 expressing cells by acting on viral entry.
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.
Unité Interactions Moléculaires Flavivirus-Hôtes, Institut Pasteur, 75724 Paris, France.
Hans
H
Henrik Gad
Sylvie
S
Paulous
Essia
E
Belarbi
Laure
L
Diancourt
Christian
C
Drosten
Beate M
BM
Kümmerer
Aileen E
AE
Plate
Valérie
V
Caro
Philippe
P
Desprès
D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis* / Q000276:immunology; D000818:Animals; D017209:Apoptosis; D019677:Artificial Gene Fusion; D002646:Chikungunya virus / Q000235:genetics / Q000254:growth & development / Q000276:immunology / Q000502:physiology*; D017930:Genes, Reporter; D006367:HeLa Cells; D006801:Humans; D008156:Luciferases / Q000032:analysis / Q000235:genetics; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D032446:Myoblasts / Q000502:physiology / Q000821:virology; D048790:Renilla / Q000201:enzymology; D014764:Viral Proteins / Q000235:genetics* / Q000378:metabolism*; D053586:Virus Internalization
D050505:Mutant Proteins; D014764:Viral Proteins; D008156:Luciferases; D015088:2',5'-Oligoadenylate Synthetase; C577439:OAS3 protein, human