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.
Fish Shellfish Immunol. 2021 Apr;111:83-93. doi: 10.1016/j.fsi.2021.01.006. Epub 2021 Jan 26.
Tumor necrosis factor receptor 1 (TNFR1) associated death domain protein (TRADD) is a pivotal adaptor in TNF signaling pathway and up-regulates MAVS/IFN signaling pathway in human and mammal. However, the role of TRADD in teleost fish remains obscure. To reveal the function of teleost TRADD in the innate immune response, the TRADD homologue (bcTRADD) of black carp (Mylopharyngodon piceus) has been cloned and the function of bcTRADD is investigated in this study, which shares similar functional domain to its mammalian counterpart. bcTRADD mRNA expression level increased in response to different stimuli, including LPS, poly (I:C) and virus infection in host cells. bcTRADD activated the transcriptional activity of NF-κB promoter in the reporter assay; however, showed hardly any effect on the transcriptional activity of IFN promoter. It was interesting that black carp mitochondria antiviral signaling protein (bcMAVS)-activated IFN promoter transcription were dramatically depressed by bcTRADD and the C-terminal death domain of bcTRADD was indispensable for its regulation of bcMAVS. Accordingly, the plaque assay result showed that EPC cells co-expressing bcMAVS and bcTRADD presented much attenuated antiviral activity than EPC cells expressing bcMAVS alone. Knockdown of bcTRADD slightly promoted the antiviral ability of the host cells against SVCV. The current data support the conclusion that bcTRADD suppresses MAVS-mediated antiviral signaling, which is different to its mammalian counterpart.
肿瘤坏死因子受体 1（TNFR1）相关死亡结构域蛋白（TRADD）是 TNF 信号通路中的关键衔接蛋白，可在上调人类和哺乳动物的 MAVS/IFN 信号通路。然而，TRADD 在硬骨鱼类中的作用尚不清楚。为了揭示真骨鱼类 TRADD 在先天免疫反应中的功能，本研究克隆了草鱼（Mylopharyngodon piceus）的 TRADD 同源物（bcTRADD），并研究了其功能。bcTRADD 与哺乳动物的对应物具有相似的功能结构域。bcTRADD mRNA 的表达水平在受到不同刺激时会增加，包括 LPS、poly（I:C）和病毒感染宿主细胞。bcTRADD 在报告基因检测中激活了 NF-κB 启动子的转录活性；然而，对 IFN 启动子的转录活性几乎没有影响。有趣的是，bcTRADD 显著抑制了草鱼抗病毒信号蛋白（bcMAVS）激活的 IFN 启动子转录，bcTRADD 的 C 末端死亡结构域对于其对 bcMAVS 的调控是必不可少的。相应地，噬斑试验结果表明，共表达 bcMAVS 和 bcTRADD 的 EPC 细胞的抗病毒活性明显低于单独表达 bcMAVS 的 EPC 细胞。bcTRADD 的敲低略微促进了宿主细胞对 SVCV 的抗病毒能力。目前的数据支持以下结论：bcTRADD 抑制了 bcMAVS 介导的抗病毒信号通路，这与哺乳动物的对应物不同。
