Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses.,Nature Communications

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Influenza A virus M2 protein triggers mitochondrial DNA-mediated antiviral immune responses.
Nature Communications ( IF 14.7 ) Pub Date : 2019-10-11 , DOI: 10.1038/s41467-019-12632-5
Miyu Moriyama _{1,

2,

3} , Takumi Koshiba ₂ , Takeshi Ichinohe ₁

Affiliation

Cytosolic mitochondrial DNA (mtDNA) activates cGAS-mediated antiviral immune responses, but the mechanism by which RNA viruses stimulate mtDNA release remains unknown. Here we show that viroporin activity of influenza virus M2 or encephalomyocarditis virus (EMCV) 2B protein triggers translocation of mtDNA into the cytosol in a MAVS-dependent manner. Although influenza virus-induced cytosolic mtDNA stimulates cGAS- and DDX41-dependent innate immune responses, the nonstructural protein 1 (NS1) of influenza virus associates with mtDNA to evade the STING-dependent antiviral immunity. The STING-dependent antiviral signaling is amplified in neighboring cells through gap junctions. In addition, we find that STING-dependent recognition of influenza virus is essential for limiting virus replication in vivo. Our results show a mechanism by which influenza virus stimulates mtDNA release and highlight the importance of DNA sensing pathway in limiting influenza virus replication.

中文翻译：

甲型流感病毒M2蛋白触发线粒体DNA介导的抗病毒免疫反应。

胞质线粒体DNA（mtDNA）激活cGAS介导的抗病毒免疫反应，但RNA病毒刺激mtDNA释放的机制仍然未知。在这里，我们显示流感病毒M2或脑心肌炎病毒（EMCV）2B蛋白的viroporin活性以依赖MAVS的方式触发mtDNA进入细胞质。尽管流感病毒诱导的胞质mtDNA刺激了cGAS和DDX41依赖的先天免疫应答，但是流感病毒的非结构蛋白1（NS1）与mtDNA结合，逃避了STING依赖的抗病毒免疫。STING依赖的抗病毒信号通过间隙连接在相邻细胞中扩增。此外，我们发现流感病毒的STING依赖性识别对于限制体内病毒复制至关重要。

更新日期：2019-10-12

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