title: Higher antiviral response of RIG-I through enhancing RIG-I/MAVS-mediated signaling by its long insertion variant in zebrafish.
abstract: As an intracellular pattern recognition receptor (PRR), the retinoic acid-inducible gene-I (RIG-I) is responsible for the recognition of cytosolic viral nucleic acids and the production of type I interferons (IFNs). In the present study, an insertion variant of RIG-I with 38 amino acids inserted in the N-terminal CARD2 domain, as well as the typical type, named as RIG-Ia and RIG-Ib respectively were identified in zebrafish. RIG-Ia and RIG-Ib were all up-regulated following the infection of a negative ssRNA virus, the Spring Viremia of Carp Virus (SVCV), and an intracellular Gram-negative bacterial pathogen Edwardsiella tarda, indicating the RLR may have a role in the recognition of both viruses and bacteria. The over-expression of RIG-Ib in cultured fish cells resulted in significant increase in type I IFN promoter activity, and in protection against SVCV infection, whereas the over-expression of RIG-Ia had no direct effect on IFN activation nor antiviral response. Furthermore, it was revealed that both RIG-Ia and RIG-Ib were associated with the downstream molecular mitochondrial antiviral signaling protein, MAVS, and interestingly RIG-Ia when co-transfected with RIG-Ib or MAVS, induced a significantly higher level of type I IFN promoter activity and the expression level of Mx and IRF7, implying that the RIG-Ia may function as an enhancer in the RIG-Ib/MAVS-mediated signaling pathway.
authors.affiliation: College of Fisheries, Jimei University, 43 Yindou Road, Xiamen, Fujian Province, 361021, China; State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China.
authors.forename: Peng Fei
authors.initials: PF
authors.lastname: Zou
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China. Electronic address: mingxianchang@ihb.ac.cn.
authors.forename: Ming Xian
authors.initials: MX
authors.lastname: Chang
authors.affiliation: School of Environmental Science and Engineering, Huazhong University of Science and Technology, Wuhan, Hubei Province, 430074, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Huan Zhang
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China.
authors.forename: Jian Ping
authors.initials: JP
authors.lastname: Fu
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China.
authors.forename: Shan Nan
authors.initials: SN
authors.lastname: Chen
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province, 430072, China. Electronic address: pinnie@ihb.ac.cn.
authors.forename: Pin
authors.initials: P
authors.lastname: Nie
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000998:Antiviral Agents / Q000378:metabolism; D002460:Cell Line; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000235:genetics / Q000378:metabolism; D020609:Edwardsiella tarda / Q000502:physiology; D004756:Enterobacteriaceae Infections / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D005393:Fish Diseases / Q000235:genetics* / Q000378:metabolism / Q000821:virology; D005786:Gene Expression Regulation; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012209:Rhabdoviridae / Q000502:physiology; D018353:Rhabdoviridae Infections / Q000235:genetics / Q000378:metabolism / Q000662:veterinary* / Q000821:virology; D016415:Sequence Alignment / Q000662:veterinary; D015398:Signal Transduction; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D000998:Antiviral Agents; D018076:DNA, Complementary; D007370:Interferon Type I; D012333:RNA, Messenger; D029961:Zebrafish Proteins; C000599980:ddx58 protein, zebrafish
keywords: Mitochondrial antiviral signaling protein; RIG-Ib/MAVS-mediated signaling pathway; Retinoic acid-inducible gene-I; Type I IFN production; Variant