SNX8 modulates the innate immune response to RNA viruses by regulating the aggregation of VISA
SNX8 modulates the innate immune response to RNA viruses by regulating the aggregation of VISA
复制标题
SNX8 通过调节 VISA 的聚集来调节对 RNA 病毒的先天免疫反应
DOI：
10.1038/s41423-019-0285-2
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发表时间：
2020-11-01
影响因子：
24.1
通讯作者：
Yang, Qing
中科院分区：
文献类型：
--
作者：
Guo, Wei;Wei, Jin;Yang, Qing
线粒体病毒诱导的信号转导衔接子（VISA，也称为线粒体抗病毒信号转导，MAVS）蛋白是对胞质病毒RNA的先天免疫应答中的中心衔接子。病毒感染引起VISA的聚集，这对其下游信号组分的募集很重要。如何管理VISA聚合仍然未知。在这里，我们发现分选连接蛋白8（SNX 8）是RNA病毒触发的下游效应基因和先天免疫反应的诱导的正调节因子。与野生型小鼠相比，感染RNA病毒的Snx 8（-/-）小鼠的大脑和肺部表现出较低的血清细胞因子水平和较高的病毒滴度，从而导致更高的致死率。从机制上讲，病毒感染诱导SNX 8从胞质溶胶易位到线粒体及其与VISA的缔合增加，导致VISA聚集，其募集下游信号传导组分并诱导下游抗病毒基因。我们的研究结果表明，SNX 8是RIG-I样受体（RLR）介导的先天性免疫反应的关键组成部分，通过调节VISA聚集和激活。
The mitochondrial virus-induced signaling adaptor (VISA, also called mitochondrial antiviral signaling, MAVS) protein is a central adaptor in the innate immune response to cytosolic viral RNA. Viral infection causes the aggregation of VISA, which is important for its recruitment of downstream signaling components. How VISA aggregation is regulated remains unknown. Here, we found that sorting nexin 8 (SNX8) is a positive regulator of the RNA virus-triggered induction of downstream effector genes and innate immune response. The brains and lungs of Snx8(-/-) mice infected with RNA viruses exhibited lower serum cytokine levels and higher viral titers than those of wild-type mice, resulting in higher lethality. Mechanistically, viral infection induced the translocation of SNX8 from the cytosol to mitochondria and its increased association with VISA, leading to VISA aggregation, its recruitment of downstream signaling components and the induction of downstream antiviral genes. Our findings suggest that SNX8 is a critical component of the RIG-I-like receptor (RLR)-mediated innate immune response by modulating VISA aggregation and activation.