title: Involvement of zebrafish RIG-I in NF-κB and IFN signaling pathways: insights into functional conservation of RIG-I in antiviral innate immunity.
abstract: The retinoic acid-inducible gene I (RIG-I) is a critical sensor for host recognition of RNA virus infection and initiation of antiviral signaling pathways in mammals. However, data on the occurrence and functions of this molecule in lower vertebrates are limited. In this study, we characterized an RIG-I homolog (DrRIG-I) from zebrafish. Structurally, this DrRIG-I shares a number of conserved functional domains/motifs with its mammalian counterparts, namely, caspase activation and recruitment domain, DExD/H box, a helicase domain, and a C-terminal domain. Functionally, stimulation with DrRIG-I CARD in zebrafish embryos significantly activated the NF-κB and IFN signaling pathways, leading to the expression of TNF-α, IL-8 and IFN-induced Mx, ISG15, and viperin. However, knockdown of TRIM25 (a pivotal activator for RIG-I receptors) significantly suppressed the induced activation of IFN signaling. Results suggested the functional conservation of RIG-I receptors in the NF-κB and IFN signaling pathways between teleosts and mammals, providing a perspective into the evolutionary history of RIG-I-mediated antiviral innate immunity.
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Li
authors.initials: L
authors.lastname: Nie
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Ying-sheng
authors.initials: YS
authors.lastname: Zhang
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China.
authors.forename: Wei-ren
authors.initials: WR
authors.lastname: Dong
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China. Electronic address: xianglx@zju.edu.cn.
authors.forename: Li-xin
authors.initials: LX
authors.lastname: Xiang
authors.affiliation: College of Life Sciences, Zhejiang University, Hangzhou 310058, China; Key Laboratory for Cell and Gene Engineering of Zhejiang Province, Hangzhou 310058, China. Electronic address: shaojz@zju.edu.cn.
authors.forename: Jian-zhong
authors.initials: JZ
authors.lastname: Shao
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D053468:CARD Signaling Adaptor Proteins / Q000096:biosynthesis / Q000378:metabolism; D053487:DEAD-box RNA Helicases; D005260:Female; D005393:Fish Diseases / Q000276:immunology; D055785:Gene Knockdown Techniques; D007113:Immunity, Innate / Q000276:immunology; D007372:Interferons / Q000378:metabolism*; D016209:Interleukin-8 / Q000096:biosynthesis; D008297:Male; D008969:Molecular Sequence Data; D060172:Morpholinos / Q000235:genetics; D064547:Myxovirus Resistance Proteins / Q000096:biosynthesis; D016328:NF-kappa B / Q000378:metabolism*; D012327:RNA Virus Infections / Q000276:immunology* / Q000821:virology; D012328:RNA Viruses / Q000276:immunology; D016415:Sequence Alignment; D017422:Sequence Analysis, DNA; D014157:Transcription Factors / Q000235:genetics; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D015027:Zebrafish / Q000276:immunology* / Q000821:virology; D029961:Zebrafish Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D053468:CARD Signaling Adaptor Proteins; D016209:Interleukin-8; D060172:Morpholinos; D064547:Myxovirus Resistance Proteins; D016328:NF-kappa B; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; D029961:Zebrafish Proteins; C000599980:ddx58 protein, zebrafish; D007372:Interferons; D053487:DEAD-box RNA Helicases
keywords: IFN signaling pathway; NF-κB signaling pathway; TRIM25 regulation; Zebrafish RIG-I