The 2',5'-oligoadenylate synthetase 1b is a potent inhibitor of West Nile virus replication inside infected cells.
The 2',5'-oligoadenylate synthetase (OAS) proteins associated with endoribonuclease RNase L are components of the interferon-regulated OAS/RNase L system, which is an RNA decay pathway known to play an important role in the innate antiviral immunity. A large body of evidence suggests a critical role for the 1b isoform of the mouse Oas gene (Oas1b) in resistance to West Nile virus (WNV) infection in vivo. WNV is a positive, single-stranded RNA virus responsible for severe encephalitis in a large range of animal species and humans. To investigate the molecular basis for the sensitivity of WNV to the Oas1b antiviral pathway, we established a stable mouse fibroblastic cell clone that up-regulates Oas1b protein expression under the control of the Tet-Off expression system. We showed that murine cells respond to Oas1b expression by efficiently inhibiting WNV replication. The antiviral action of Oas1b was essentially restricted to the early stages in virus life cycle. We found that the inability of WNV to productively infect the Oas1b-expressing cells was attributable to a dramatic reduction in positive-stranded viral RNA level. Thus, Oas1b represents an antiviral pathway that exerts its inhibitory effect on WNV replication by preventing viral RNA accumulation inside infected cells.
Kajaste-Rudnitski
Anna
A
Interactions Moléculaires Flavivirus-Hôtes and Génétique des Mammifères, Institut Pasteur, 25 Rue du Dr. Roux, 75724 Paris, Cedex 15, France.
Mashimo
Tomoji
T
Frenkiel
Marie-Pascale
MP
Guénet
Jean-Louis
JL
Lucas
Marianne
M
Desprès
Philippe
P
D015088:2',5'-Oligoadenylate Synthetase / Q000502:physiology*; D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001483:Base Sequence; D015139:Blotting, Southern; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival; D009033:Culicidae / Q000821:virology; D017931:DNA Primers / Q000737:chemistry; D004722:Endoribonucleases / Q000737:chemistry / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D007109:Immunity; D047468:Immunoprecipitation; D007372:Interferons / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D011480:Protease Inhibitors / Q000494:pharmacology; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D012367:RNA, Viral / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D013778:Tetrazolium Salts / Q000494:pharmacology; D013844:Thiazoles / Q000494:pharmacology; D014162:Transfection; D014779:Virus Replication; D014901:West Nile Fever / Q000473:pathology* / Q000517:prevention & control*; D014902:West Nile virus / Q000187:drug effects* / Q000235:genetics
D000998:Antiviral Agents; D017931:DNA Primers; D011480:Protease Inhibitors; D012367:RNA, Viral; D013778:Tetrazolium Salts; D013844:Thiazoles; D007372:Interferons; C509914:Oas1b protein, mouse; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D046988:Proteasome Endopeptidase Complex; C022616:thiazolyl blue