Zebrafish RBM47 Promotes Lysosome-Dependent Degradation of MAVS to Inhibit IFN Induction
Zebrafish RBM47 Promotes Lysosome-Dependent Degradation of MAVS to Inhibit IFN Induction
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斑马鱼 RBM47 促进 MAVS 的溶酶体依赖性降解以抑制 IFN 诱导
DOI：
10.4049/jimmunol.1901387
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发表时间：
2020-10-01
影响因子：
4.4
通讯作者：
Li, Shun
中科院分区：
文献类型：
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作者：
Lu, Long-Feng;Zhang, Can;Li, Shun
关键点斑马鱼RBM47负性调节RLR介导的干扰素的产生。RBM47以溶酶体依赖的方式与MAV相互作用并降解MAV。干扰素对于宿主抵御病毒入侵是必不可少的，而它必须受到严格的调控，以防止过度免疫反应。鱼类线粒体抗病毒信号蛋白(MAVS)是干扰素产生的重要因子，但到目前为止，关于MAVS对干扰素的调控机制研究较少。在这项研究中，我们发现斑马鱼RNA结合基序蛋白47(RBM47)以溶酶体依赖的方式促进MAV的降解，从而抑制干扰素的产生。首先，RBM47显著抑制了多聚肌苷/多胞苷(PolyI：C)、鲤鱼病毒春季病毒血症或视黄酸诱导基因I(RIG-I)样受体途径成分激活的干扰素的转录。其次，RBM47与MAV相互作用，促进了MAV的溶酶体依赖性降解，使MAV的细胞定位从胞浆向溶酶体区转移。最后，RBM47抑制了下游MITA和IRF3/7的激活，损害了宿主的抗病毒反应。综上所述，这些数据表明，斑马鱼RBM47通过促进溶酶体依赖的MAV降解来负面调节干扰素的产生，为深入了解RBM47在鱼类先天抗病毒免疫反应中的作用提供了见解。
Key Points Zebrafish RBM47 negatively regulates RLR-mediated IFN production. RBM47 interacts with and degrades MAVS in a lysosome-dependent manner. IFN is essential for hosts to defend against viral invasion, whereas it must be tightly regulated to prevent hyperimmune responses. Fish mitochondrial antiviral signaling protein (MAVS) is a vital factor for IFN production, but until now, there have been few studies on the regulation mechanisms of fish MAVS enabling IFN to be properly controlled. In this study, we show that zebrafish RNA-binding motif protein 47 (RBM47) promotes MAVS degradation in a lysosome-dependent manner to suppress IFN production. First, the transcription of IFN activated by polyinosinic/polycytidylic acid (poly I:C), spring viremia of carp virus, or retinoic acid–inducible gene I (RIG-I)–like receptor pathway components were significantly suppressed by RBM47. Second, RBM47 interacted with MAVS and promoted lysosome-dependent degradation of MAVS, changing the cellular location of MAVS from the cytoplasm to the lysosome region. Finally, RBM47 inhibited downstream MITA and IRF3/7 activation, impairing the host antiviral response. Collectively, these data suggest that zebrafish RBM47 negatively regulates IFN production by promoting lysosome-dependent degradation of MAVS, providing insights into the role of RBM47 in the innate antiviral immune response in fish.