【作者】 胡祎玮； 武小曼； 任诗思； 聂品； 昌鸣先；

【Author】 HU Yiwei;WU Xiaoman;REN Shisi;NIE Pin;CHANG Mingxian;State Key Laboratory of Freshwater Ecology and Biotechnology, Institute of Hydrobiology, Chinese Academy of Sciences;

【机构】 中国科学院水生生物研究所淡水生态与生物技术国家重点实验室；

【摘要】 TBK1对天然免疫中IRF3的磷酸化起到重要的调控作用,从而影响Ⅰ型干扰素的表达。在此研究中,我们克隆得到斑马鱼TBK1基因的两个剪接异构体,将其命名为TBK1-tv1,TBK1-tv2。与TBK1相比,TBK1-tv1缺失第3-4个外显子,而TBK1-tv2缺失了第4-18个外显子。这两个异构体不能像TBK1那样显著抑制SVCV的增殖;同时,SVCV病毒的感染不能诱导它们的表达。过表达TBK1的剪接异构体能显著下调RIG-I、MAVS、TBK1以及IRF3诱导的Ⅰ型干扰素启动子的活性。荧光定量结果表明,TBK1的剪接异构体能显著抑制MAVS以及TBK1诱导的干扰素以及干扰素诱导相关基因的表达。这些研究结果揭示了TBK1的剪接异构体在Ⅰ型干扰素信号通路中起着负调控的作用。更多还原

【Abstract】 TBK1 has a pivotal role in regulating the phosphorylating of IRF3 in the innate immune response, thus influences the expression of type I IFNs. In this study, we identified two TBK1 variants from zebrafish and named them as TBK1_tv1 and TBK1_tv2. Compared with TBK1, TBK1_tv1 lacks exons 3-4, while TBK1_tv2 lacks exons 4-18. We found that SVCV infection can not induce the expression of TBK1 variants, and that TBK1 variants have no role for viral replication. Furthermore, overexpression of TBK1_tv1 and TBK1_tv2 can significantly inhibit the activity of IFN1 or IFN3 promoters, which is induced by RIG-I, MAVS, TBK1 and TRF3. Realtime PCR indicated that overexpression of TBK1_tv1 and TBK1_tv2 significantly decreased the production of IFN1 and IFN-stimulated genes induced by MAVS and TBK1. These data provide evidence that TBK1 variants act as negative regulators in the type Ⅰ IFN signaling pathway.更多还原