ZNF205通过靶向RIG-I正调控RLR抗病毒信号通路

ZNF205 positively regulates RLR antiviral signaling by targeting RIG-I

目的探究ZNF205(zinc finger protein 205)对RIG-I(retinoic acid-inducible gene I)介导的RLR(RIG-I like receptors,RLRs)抗病毒信号通路的影响。方法采用免疫共沉淀、免疫印迹、非变性聚丙烯酰胺凝胶电泳、双荧光素酶报告基因实验、实时荧光定量PCR、病毒空斑等实验探索ZNF205在RLRs信号通路中的作用。结果ZNF205与RIG-I相互作用。过表达ZNF205促进了SeV诱导的IRF3(interferon regulatory factor 3)的二聚化,也增强了RIG-I-N(aa1-284)介导或SeV诱导的IFN-β(interferon beta)启动子的活性,同时还增强了SeV诱导的IFN-β的转录。病毒空斑实验结果显示过表达ZNF205能够抑制病毒的复制。研究结果还表明,ZNF205促进RIG-I的泛素化修饰以及RIG-I的K63泛素化修饰。结论ZNF205在RLR抗病毒先天免疫信号通路中起正调控作用。

The study was performed to explore the effect of ZNF205 on RIG-I-mediated RLR antiviral innate immunity.The role of ZNF205 in RLRs signaling pathway were evaluated by using immunoprecipitation,immunoblotting,native PAGE(polyacrylamide gel electrophoresis),dual luciferase reporter assay,real-time fluorescence quantitative PCR,and plaque assay.Our data showed that ZNF205 could interact with RIG-I.Overexpression of ZNF205 enhanced SeV-induced dimerization of IRF3,and also promoted SeV-induced or RIGI-N(aa1-284)-mediated IFN-βpromoter activity and SeV-induced transcription of IFN-β.Plaque assay also verified that overexpression of ZNF205 inhibited virus replication.In addition,ZNF205 promoted the ubiquitination modification of RIG-I as well as K63-linked ubiquitination of RIG-I.Thus,ZNF205 is a positive regulator in the RLR antiviral innate immune signaling pathway.