Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex.
Severe acute respiratory syndrome coronavirus M protein inhibits type I interferon production by impeding the formation of TRAF3.TANK.TBK1/IKKepsilon complex.
复制标题
严重的急性呼吸综合征冠状病毒M蛋白通过阻碍Traf3.tank.tbk1/ikkepsilon Complex的形成，抑制I型干扰素的产生。
DOI：
10.1074/jbc.m109.008227
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发表时间：
2009-06-12
期刊：
影响因子：
--
通讯作者：
Jin DY
中科院分区：
文献类型：
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作者：
Siu KL;Kok KH;Ng MJ;Poon VKM;Yuen KY;Zheng BJ;Jin DY
严重急性呼吸综合征(SARS)冠状病毒在人类中具有高致病性，并在多个水平上逃避天然免疫。它已经进化出各种策略来对抗I型干扰素的产生和作用，这些策略动员了对病毒感染的一线防御。在这项研究中，我们证明了SARS冠状病毒M蛋白抑制I型干扰素的基因转录。M蛋白通过双链核糖核酸、RIG-I、MDA5、Tbk1、IKKϵ和病毒诱导的信号转接子(VISA)有效地拮抗干扰素刺激的反应元件依赖转录的激活，但当IRF3或IRF7过表达时，M蛋白对该元件的转录活性没有影响。M蛋白在物理上与RIG-I、Tbk1、IKKϵ和TRAF3结合，可能将它们中的一些隔离在膜相关的细胞质隔间中。因此，M蛋白的表达阻止了TRAF3·TANK·TbK1/IKKϵ复合体的形成，从而抑制了TbK1/IKKϵ依赖的转录因子的激活。综上所述，我们的发现揭示了SARS冠状病毒绕过I型干扰素产生的新机制。
Severe acute respiratory syndrome (SARS) coronavirus is highly pathogenic in humans and evades innate immunity at multiple levels. It has evolved various strategies to counteract the production and action of type I interferons, which mobilize the front-line defense against viral infection. In this study we demonstrate that SARS coronavirus M protein inhibits gene transcription of type I interferons. M protein potently antagonizes the activation of interferon-stimulated response element-dependent transcription by double-stranded RNA, RIG-I, MDA5, TBK1, IKKϵ, and virus-induced signaling adaptor (VISA) but has no influence on the transcriptional activity of this element when IRF3 or IRF7 is overexpressed. M protein physically associates with RIG-I, TBK1, IKKϵ, and TRAF3 and likely sequesters some of them in membrane-associated cytoplasmic compartments. Consequently, the expression of M protein prevents the formation of TRAF3·TANK·TBK1/IKKϵ complex and thereby inhibits TBK1/IKKϵ-dependent activation of IRF3/IRF7 transcription factors. Taken together, our findings reveal a new mechanism by which SARS coronavirus circumvents the production of type I interferons.