State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, 410081, China.
State Key Laboratory of Developmental Biology of Freshwater Fish, College of Life Science, Hunan Normal University, Changsha, 410081, China; College of Fisheries, Huazhong Agricultural University, Wuhan, 430070, China.
Dev Comp Immunol. 2021 Aug;121:104073. doi: 10.1016/j.dci.2021.104073. Epub 2021 Mar 22.
TRIF is an antiviral adaptor downstream of Toll-like receptors, the roles of teleost TRIF and their regulation remain largely unknown. In this study, a TRIF homologue (bcTRIF) of black carp (Mylopharyngodon piceus) has been cloned, and the transcription of bcTRIF in vivo and ex vivo increased in response to different stimuli. Overexpressed bcTRIF induced the transcription of interferon promoter in the EPC cells and enhanced protection of cells against infection of spring viremia of carp virus (SVCV). The previous study has identified that black carp TRAF2 (bcTRAF2) and TRAF6 (bcTRAF6) functioned positively in RIG-I/MAVS signaling. When co-expressed with bcTRAF2, bcTRIF-induced the transcription of interferon promoter in EPC cells was decreased, and the antiviral activity of bcTRIF was dampened accordingly. On the contrary, co-expressed bcTRAF6 enhanced both bcTRIF-mediated interferon promoter transcription and antiviral activity. The subsequent co-immunoprecipitation identified the interaction between bcTRAF2/6 and bcTRIF. Thus, bcTRIF-mediated antiviral signaling is up-regulated by bcTRAF6 and down-regulated by bcTRAF2.
TRIF 是 Toll 样受体下游的抗病毒衔接蛋白，硬骨鱼类 TRIF 的作用及其调控仍知之甚少。本研究克隆了草鱼（Mylopharyngodon piceus）的 TRIF 同源物（bcTRIF），并发现 bcTRIF 在体内和体外对不同刺激的转录增加。过表达的 bcTRIF 诱导 EPC 细胞中干扰素启动子的转录，并增强了细胞对鲤鱼春病毒血症病毒（SVCV）感染的保护。先前的研究已经确定草鱼 TRAF2（bcTRAF2）和 TRAF6（bcTRAF6）在 RIG-I/MAVS 信号通路中发挥正向作用。当与 bcTRAF2 共表达时，bcTRIF 在 EPC 细胞中诱导的干扰素启动子转录减少，相应地，bcTRIF 的抗病毒活性减弱。相反，共表达 bcTRAF6 增强了 bcTRIF 介导的干扰素启动子转录和抗病毒活性。随后的免疫共沉淀鉴定了 bcTRAF2/6 和 bcTRIF 之间的相互作用。因此，bcTRIF 介导的抗病毒信号转导被 bcTRAF6 上调，被 bcTRAF2 下调。
