The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation.
The PB1 protein of influenza A virus inhibits the innate immune response by targeting MAVS for NBR1-mediated selective autophagic degradation.
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甲型流感病毒的PB1蛋白通过靶向MAVS进行NBR1介导的选择性自噬降解来抑制先天免疫反应
DOI：
10.1371/journal.ppat.1009300
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发表时间：
2021-03
期刊：
影响因子：
6.7
通讯作者：
Zhu Q
中科院分区：
文献类型：
--
作者：
Zeng Y;Xu S;Wei Y;Zhang X;Wang Q;Jia Y;Wang W;Han L;Chen Z;Wang Z;Zhang B;Chen H;Lei CQ;Zhu Q
甲型流感病毒（Influenza A virus，IAV）已经进化出多种策略来利用不同的病毒蛋白来抵消先天性免疫应答。然而，该机制尚未完全阐明。在这项研究中，我们确定了PB 1蛋白的H7N9病毒作为一个新的负调节病毒或聚（I：C）刺激的IFN诱导和特异性相互作用，并不稳定的MAVS。随后的研究表明，PB 1促进E3连接酶RNF 5催化MAVS在Lys 362和Lys 461处的K27连接的多泛素化。此外，我们发现PB 1优先与BRCA 1（NBR 1）的选择性自噬受体相邻结合，该受体识别泛素化的MAVS并将其递送至自噬体进行降解。PB 1介导的降解级联通过阻断RIG-I-MAVS介导的先天信号传导途径促进H7N9病毒感染。总而言之，这些数据揭示了涉及PB 1-RNF 5-MAVS-NBR 1轴的负调节机制，并提供了对流感病毒采用的涉及选择性自噬和先天信号通路的逃避策略的见解。
Influenza A virus (IAV) has evolved various strategies to counteract the innate immune response using different viral proteins. However, the mechanism is not fully elucidated. In this study, we identified the PB1 protein of H7N9 virus as a new negative regulator of virus- or poly(I:C)-stimulated IFN induction and specifically interacted with and destabilized MAVS. A subsequent study revealed that PB1 promoted E3 ligase RNF5 to catalyze K27-linked polyubiquitination of MAVS at Lys362 and Lys461. Moreover, we found that PB1 preferentially associated with a selective autophagic receptor neighbor of BRCA1 (NBR1) that recognizes ubiquitinated MAVS and delivers it to autophagosomes for degradation. The degradation cascade mediated by PB1 facilitates H7N9 virus infection by blocking the RIG-I-MAVS-mediated innate signaling pathway. Taken together, these data uncover a negative regulatory mechanism involving the PB1-RNF5-MAVS-NBR1 axis and provide insights into an evasion strategy employed by influenza virus that involves selective autophagy and innate signaling pathways.
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作者：
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通讯作者：
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DOI：
10.1038/nrmicro3367
发表时间：
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