The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination
The Severe Acute Respiratory Syndrome Coronavirus Nucleocapsid Inhibits Type I Interferon Production by Interfering with TRIM25-Mediated RIG-I Ubiquitination
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DOI：
10.1128/jvi.02143-16
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发表时间：
2017-04-01
影响因子：
5.4
通讯作者：
Cao, Cheng
中科院分区：
文献类型：
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作者：
Hu, Yong;Li, Wei;Cao, Cheng
严重急性呼吸系统综合征（SARS）是一种由冠状病毒（SARS-CoV）引起的呼吸道疾病，其特征是非典型肺炎。SARS冠状病毒的N蛋白（Nucleocapsidprotein，N蛋白）通过一种未知的机制在抑制I型干扰素（Interferon，IFN）的产生中起重要作用。在这项研究中，SARS-CoV N蛋白被发现与三重基序蛋白25（TRIM 25）E3泛素连接酶的SPRY结构域结合，从而干扰TRIM 25和视黄酸诱导基因I（RIG-I）之间的关联，并抑制TRIM 25介导的RIG-I泛素化和激活。I型干扰素的生产诱导聚I. C或仙台病毒（SeV）被抑制的SARS-CoV N蛋白。SARS-CoV复制增加的全长N蛋白的过表达，但不是N氨基酸1至361，不能与TRIM 25相互作用。这些研究结果提供了一个深刻的解释SARS冠状病毒介导的宿主先天免疫抑制所造成的N蛋白。重要的SARS冠状病毒N蛋白是必不可少的病毒的生命周期，并在病毒-宿主相互作用中起着关键作用。我们证明了N蛋白的C端与TRIM 25的SPRY结构域之间的相互作用抑制了TRIM 25介导的RIG-I泛素化，从而导致IFN产生的抑制。我们还发现中东呼吸综合征冠状病毒（MERS-CoV）N蛋白与TRIM 25相互作用并抑制RIG-I信号传导。这些发现的结果表明冠状病毒N蛋白在调节宿主的初始先天免疫应答中的功能。
Severe acute respiratory syndrome (SARS) is a respiratory disease, caused by a coronavirus (SARS-CoV), that is characterized by atypical pneumonia. The nucleocapsid protein (N protein) of SARS-CoV plays an important role in inhibition of type I interferon (IFN) production via an unknown mechanism. In this study, the SARS-CoV N protein was found to bind to the SPRY domain of the tripartite motif protein 25 (TRIM25) E3 ubiquitin ligase, thereby interfering with the association between TRIM25 and retinoic acid-inducible gene I (RIG-I) and inhibiting TRIM25-mediated RIG-I ubiquitination and activation. Type I IFN production induced by poly I.C or Sendai virus (SeV) was suppressed by the SARS-CoV N protein. SARS-CoV replication was increased by overexpression of the full-length N protein but not N amino acids 1 to 361, which could not interact with TRIM25. These findings provide an insightful interpretation of the SARS-CoV-mediated host innate immune suppression caused by the N protein.IMPORTANCE The SARS-CoV N protein is essential for the viral life cycle and plays a key role in the virus-host interaction. We demonstrated that the interaction between the C terminus of the N protein and the SPRY domain of TRIM25 inhibited TRIM25mediated RIG-I ubiquitination, which resulted in the inhibition of IFN production. We also found that the Middle East respiratory syndrome CoV (MERS-CoV) N protein interacted with TRIM25 and inhibited RIG-I signaling. The outcomes of these findings indicate the function of the coronavirus N protein in modulating the host's initial innate immune response.