title: MAVS splicing variants contribute to the induction of interferon and interferon-stimulated genes mediated by RIG-I-like receptors.
abstract: The mitochondrial antiviral signaling protein (MAVS) plays a key role in the signal transduction of RIG-I-like receptors (RLRs)-mediated antiviral response. In the present study, zebrafish MAVS transcript variants, namely MAVS_tv1 and MAVS_tv2, were cloned from zebrafish embryos. The putative MAVS_tv1 protein (full length form) contains an N-terminal CARD domain, a central proline region, and a C-terminal transmembrane domain (TM). MAVS_tv2 is generated by a 190 bp intron fragment insertion. The putative MAVS_tv2 protein lacked TM domain due to a frame shift, with the N-terminal 303 aa residues identical to MAVS_tv1, and no sequence homology for the C-terminal 41 aa residues. Real-time PCR showed that the expression of MAVS_tv1 in ZF4 cells was higher than that of MAVS_tv2, and MAVS variants were induced by Edwardsiella tarda and SVCV infection during the early time points of infection, whereas MAVS_tv1 unchanged or MAVS_tv2 decreased at a later time point after the infection, respectively. Overexpression of MAVS_tv1 and MAVS_tv2 in fish cells conferred antiviral resistance, and activated zebrafish IFN1 and IFN3 promoters. MAVS_tv1 overexpression induced a slow (48 hpf) increased expression of IFN1, mxa, mxb, mxe and RSAD2. In contrast, MAVS_tv2 overexpression increased rapidly and transiently the expression of IFN1, IFN2, IFN3, mxc and rsad2 at 6 or 24 hpf. The simultaneous overexpression of MAVS variants and RIG-I in zebrafish embryos led to an accumulative induction of IFNs and IFN-stimulated genes including IFN1, IFN4, mxc, mxe and rsad. Furthermore, MAVS_tv1 cooperated with RIG-I in the accumulation of RIG-I transcript in a positive feedback loop; MAVS_tv2 synergized with MDA5 in the accumulation of MAVS_tv2 transcript. Collectively, these data suggest the molecular mechanisms of fish MAVS variants in antiviral immunity.
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province 430072, China; Hubei Vocational College of Bio-Technology, Wuhan, Hubei Province 430070, China.
authors.forename: Wen Qin
authors.initials: WQ
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; Graduate University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Yi Wei
authors.initials: YW
authors.lastname: Hu
authors.affiliation: 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; Graduate University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Shi Si
authors.initials: SS
authors.lastname: Ren
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province 430072, China.
authors.forename: Pin
authors.initials: P
authors.lastname: Nie
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
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics* / Q000378:metabolism; D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D004625:Embryo, Nonmammalian / Q000166:cytology / Q000196:embryology / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism / Q000382:microbiology / Q000821:virology; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D007370:Interferon Type I / Q000235:genetics* / Q000378:metabolism / Q000494:pharmacology; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017386:Sequence Homology, Amino Acid; D015027:Zebrafish / Q000196:embryology / Q000235:genetics / Q000378:metabolism; D029961:Zebrafish Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D007370:Interferon Type I; C000600526:MAVS protein, zebrafish; D029961:Zebrafish Proteins; C000599980:ddx58 protein, zebrafish
keywords: Antiviral activity; MAVS variants; RIG-I-like receptors; SVCV; Zebrafish