Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity
Influenza A virus protein PB1-F2 translocates into mitochondria via Tom40 channels and impairs innate immunity
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DOI：
10.1038/ncomms5713
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发表时间：
2014-08-01
影响因子：
16.6
通讯作者：
Koshiba, Takumi
中科院分区：
文献类型：
--
作者：
Yoshizumi, Takuma;Ichinohe, Takeshi;Koshiba, Takumi
线粒体有助于针对RNA病毒的细胞先天免疫。线粒体介导的先天免疫受募集到线粒体膜的信号分子调节，并取决于线粒体内膜电位（Δ psi（m））。在这里，我们研究的生理相关性Δ psi（m）和肠道相关的甲型流感病毒蛋白PB 1-F2的先天免疫。当在宿主细胞中表达时，PB 1-F2通过Tom 40通道完全易位到线粒体内膜空间中，并且由于Δ psi（m）降低，其积累加速线粒体片段化。相比之下，PB 1-F2变体缺乏C-末端多肽，这是经常发现的低致病性亚型，不影响线粒体功能。PB 1-F2介导的Δ psi（m）衰减抑制RIG-I信号传导途径和NLRP 3炎性体的活化。PB 1-F2易位到线粒体中与受损的细胞先天免疫密切相关，使得该易位事件成为潜在的治疗靶标。
Mitochondria contribute to cellular innate immunity against RNA viruses. Mitochondrial-mediated innate immunity is regulated by signalling molecules that are recruited to the mitochondrial membrane, and depends on the mitochondrial inner membrane potential (Delta psi(m)). Here we examine the physiological relevance of Delta psi(m) and the mitochondrial-associating influenza A viral protein PB1-F2 in innate immunity. When expressed in host cells, PB1-F2 completely translocates into the mitochondrial inner membrane space via Tom40 channels, and its accumulation accelerates mitochondrial fragmentation due to reduced Delta psi(m). By contrast, PB1-F2 variants lacking a C-terminal polypeptide, which is frequently found in low pathogenic subtypes, do not affect mitochondrial function. PB1-F2-mediated attenuation of Delta psi(m) suppresses the RIG-I signalling pathway and activation of NLRP3 inflammasomes. PB1-F2 translocation into mitochondria strongly correlates with impaired cellular innate immunity, making this translocation event a potential therapeutic target.