title: Porcine 2', 5'-oligoadenylate synthetases inhibit Japanese encephalitis virus replication in vitro.
abstract: The 2', 5'-oligoadenylate synthetases (OAS) are antiviral proteins and several isoforms have been identified as flavivirus-resistance biomarkers in human and mouse. The expression kinetics and antiviral functions of porcine OAS family (OAS1, OAS2, and OASL) in PK-15 cells following infection by Japanese encephalitis virus (JEV) were evaluated in the present study. The endogenous expression of the three OAS genes was efficiently induced by IFN-α treatment in PK-15 cells. However, expression of pOAS1 and pOAS2 responded more quickly than pOASL. Infection by JEV also induced the expression of the pOAS isoforms, but at a significantly lower level than that observed following IFN-α stimulation. Transient overexpression of pOASL and pOAS1 inhibited JEV replication more efficiently than OAS2 overexpression. Interestingly, knockdown of pOAS2 expression by siRNA treatment led to the highest increase in JEV multiplication. Co-silencing of RNase L and each pOAS revealed that the anti-JEV function of pOAS1 and pOAS2 were RNase L dependent, while the antiviral activity of pOASL was not. In conclusion, all pOAS isoforms play a significant role in the response to JEV infection, and are differentially induced by different stimuli. The alternative pathways of antiviral activity stimulated by OASL require further study.
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Zheng
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhu
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Lian
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
authors.forename: Weiting
authors.initials: W
authors.lastname: Liu
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
authors.forename: Ruibing
authors.initials: R
authors.lastname: Cao
authors.affiliation: Key Laboratory of Animal Diseases Diagnosis and Immunology, Ministry of Agriculture, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, China.
authors.forename: Puyan
authors.initials: P
authors.lastname: Chen
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004664:Encephalitis Virus, Japanese / Q000276:immunology* / Q000502:physiology*; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions; D016898:Interferon-alpha / Q000378:metabolism; D013552:Swine; D014779:Virus Replication
chemical_list: D016898:Interferon-alpha; D015088:2',5'-Oligoadenylate Synthetase; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease
keywords: 2′-5′-oligoadenylate synthetase; Japanese encephalitis virus; antiviral activity; in vitro