title: TBK1-like transcript negatively regulates the production of IFN and IFN-stimulated genes through RLRs-MAVS-TBK1 pathway.
abstract: TANK-binding kinase 1 (TBK1) is an essential serine/threonine-protein kinase required for Toll-like receptor (TLR)- and retinoic acid-inducible gene I (RIG-I) -mediated induction of type I IFN and host antiviral defense. In the present study, TBK1-like transcript, namely TBK1L, was cloned from zebrafish. Compared with TBK1, TBK1L contains an incomplete S_TKc domain, and lacks UBL_TBK1_like domain. Realtime PCR showed that TBK1L was constitutively produced in embryos, early larvae and ZF4 cells, and unchanged in ZF4 cells following SVCV infection. Overexpression of TBK1 but not TBK1L resulted in significant activation of zebrafish IFN1 and IFN3 promoters. Similarly, TBK1L had little impact on the antiviral state of the cells. However, the overexpression of TBK1L negatively regulated the induction of zebrafish IFN1 and/or IFN3 promoters mediated by the retinoic acid-inducible gene I-like receptors (RLRs), MAVS and TBK1. In addition, the overexpression of TBK1L in zebrafish embryos led to the decreased production of many IFN-stimulated genes induced by TBK1. Collectively, these data support that zebrafish TBK1L negatively regulates RLRs-MAVS-TBK1 pathway.
authors.affiliation: College of Fisheries, Huazhong Agricultural University, Wuhan, Hubei Province 430070, China; State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province 430072, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: 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; Graduate University of Chinese Academy of Sciences, Beijing 100039, China.
authors.forename: Xiao Man
authors.initials: XM
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences, Wuhan, Hubei Province 430072, China.
authors.forename: P
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: D000595:Amino Acid Sequence; D000818:Animals; D005393:Fish Diseases / Q000276:immunology* / Q000821:virology; D007113:Immunity, Innate; D007372:Interferons / Q000235:genetics* / Q000378:metabolism; D010802:Phylogeny; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D012209:Rhabdoviridae / Q000502:physiology*; D018353:Rhabdoviridae Infections / Q000276:immunology / Q000662:veterinary* / Q000821:virology; D015398:Signal Transduction; D015027:Zebrafish; D029961:Zebrafish Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism
chemical_list: D029961:Zebrafish Proteins; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; C000614241:TBK1L protein, zebrafish
keywords: IFN; Innate immune signaling; RIG-I-Like receptors; TBK1; TBK1-like transcript; Zebrafish