title: Analysis of the Relationship Between Enzymatic and Antiviral Activities of the Chicken Oligoadenylate Synthetase-Like.
abstract: The oligoadenylate synthetase (OAS) is well known as an antiviral factor against the flavivirus infection in mammals. It is known that the oligoadenylate synthetase-like (ChOAS-L) gene is only present in the chicken genome. It has been shown in the previous report that the ChOAS-L possesses enzymatic activity to convert ATP into 2'-5'-linked oligoadenylates and antiviral activity against West Nile virus (WNV) replicon. Therefore, this study aimed to investigate the relationship between enzymatic and antiviral activities of ChOAS-L. Eight mutated ChOAS-L proteins were generated using either the site-directed mutagenesis or standard polymerase chain reaction protocol. The wild-type and mutated proteins were ectopically expressed in 293FT cells to analyze the enzymatic activity and in BHK-21 and BALB/3T3 cells to analyze the antiviral activity using WNV replicon. The results revealed that all mutated proteins showed no enzymatic activity except for ChOAS-L-AΔUbL2. However, all mutated proteins showed antiviral activity to inhibit the replication of the WNV replicon except for ChOAS-L-AΔUbL1/UbL2, which showed a partial inhibition compared to the wild-type ChOAS-L-A or other mutated proteins. These results suggest that the ChOAS-L expresses the antiflavivirus activity in a manner independent of enzymatic activity. Our results propose reconsideration of the mechanism of antiviral activity against the flavivirus replication of ChOAS-L.
authors.affiliation: 1 Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University , Sapporo, Japan .|2 Poultry Production Department, Faculty of Agriculture, Mansoura University , Mansoura, Egypt .
authors.forename: Hassan T
authors.initials: HT
authors.lastname: Tag-El-Din-Hassan
authors.affiliation: 1 Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University , Sapporo, Japan .
authors.forename: Nobuya
authors.initials: N
authors.lastname: Sasaki
authors.affiliation: 1 Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University , Sapporo, Japan .
authors.forename: Daisuke
authors.initials: D
authors.lastname: Torigoe
authors.affiliation: 1 Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University , Sapporo, Japan .
authors.forename: Masami
authors.initials: M
authors.lastname: Morimatsu
authors.affiliation: 1 Laboratory of Laboratory Animal Science and Medicine, Department of Disease Control, Graduate School of Veterinary Medicine, Hokkaido University , Sapporo, Japan .
authors.forename: Takashi
authors.initials: T
authors.lastname: Agui
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism* / Q000494:pharmacology; D002460:Cell Line; D002645:Chickens; D004789:Enzyme Activation; D015870:Gene Expression; D054884:Host-Pathogen Interactions / Q000235:genetics; D006801:Humans; D008826:Microbial Sensitivity Tests; D009154:Mutation; D055550:Protein Stability; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects; D014902:West Nile virus / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D011993:Recombinant Fusion Proteins; D015088:2',5'-Oligoadenylate Synthetase
keywords: IFNs and cytokines; OAS/RNase L; antiviral actions; infectious disease