Negatively regulation of MAVS-mediated antiviral innate immune response by E3 ligase RNF5 in black carp.
Negatively regulation of MAVS-mediated antiviral innate immune response by E3 ligase RNF5 in black carp.
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DOI：
10.1016/j.fsi.2023.108583
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发表时间：
2023-02
影响因子：
4.7
通讯作者：
Jun Yan;Guo-Bing Qiao;Enhui Wang;Yuqing Peng;Jiamin Yu;Hui-na Wu;Meiling Liu;Jiagang Tu;Yongan Zhang;Hao Feng
中科院分区：
文献类型：
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作者：
Jun Yan;Guo-Bing Qiao;Enhui Wang;Yuqing Peng;Jiamin Yu;Hui-na Wu;Meiling Liu;Jiagang Tu;Yongan Zhang;Hao Feng
线粒体抗病毒信号蛋白 (MAVS) 是 RIG-I 样受体 (RLR) 信号传导的衔接子，在宿主抗病毒先天免疫激活过程中干扰素 (IFN) 的产生中发挥关键作用。 MAVS 进行了微调，以避免产生过量的 IFN，这已在人类和哺乳动物中进行了广泛的研究。然而，硬骨鱼中 MAVS 的调控仍不清楚。在这篇手稿中，我们克隆了青鱼（青鱼）的无名指蛋白 5 (bcRNF5)，并将这种硬骨鱼 E3 泛素连接酶描述为 MAVS 的负调节因子。 bcRNF5的编码区由615个核苷酸组成，编码205个氨基酸，包含两个跨膜结构域(TM)和一个环指结构域(RING)。 bcRNF5 的转录调控在宿主细胞中因 LPS、聚 (I:C)、草鱼呼肠孤病毒 (GCRV) 和鲤鱼春季病毒血症病毒 (SVCV) 的刺激而发生变化。在免疫印迹 (IB) 测定中，bcRNF5 迁移约 22 KDa，并通过免疫荧光 (IF) 染色测试主要分布在细胞质中。此外，bcRNF5 显着抑制 bcMAVS 介导的 IFN 启动子转录。此外，IF 和免疫共沉淀测定均表明 bcRNF5 与 bcMAVS 相互作用。此外，bcRNF5 明显损害了 bcMAVS 介导的抗病毒能力。综上所述，这些结果得出结论，bcRNF5 作为 MAVS 介导的 IFN 信号传导的负调节因子，可能在青鱼病毒感染后的宿主保护中发挥关键作用。
Mitochondrial antiviral signaling protein (MAVS) is as an adaptor in RIG-I like receptor (RLR) signaling, which plays the key role in interferon (IFN) production during host antiviral innate immune activation. MAVS is fine tuned to avoid excess IFN production, which have been extensively studied in human and mammals. However, the regulation of MAVS in teleost still remains obscure. In this manuscript, we cloned ring finger protein 5 (bcRNF5) of black carp (Mylopharyngodon piceus) and characterized this teleost E3 ubiquitin ligase as a negative regulator of MAVS. The coding region of bcRNF5 consists of 615 nucleotides which encode 205 amino acids, containing twotrans-membrane domain (TM) and a ring-finger domain (RING). The transcription regulation of bcRNF5 varies in host cells in response to stimulations of LPS, poly (I:C), grass carp reovirus (GCRV) and spring viremia of carp virus (SVCV). bcRNF5 migrates around 22 KDa in immunoblot (IB) assay and distributes mainly in cytoplasm by immunofluorescent (IF) staining test. Moreover, bcRNF5 significantly inhibits bcMAVS-mediated IFN promoter transcription. In addition, both IF and co-immunoprecipitation assay showed that bcRNF5 interacts with bcMAVS. Furthermore, bcMAVS-mediated antiviral ability is distinctly impaired by bcRNF5. Taken together, these results conclude that bcRNF5, as a negative regulator of the MAVS-mediated IFN signaling, may play a key role in host protection upon virus infection in black carp.