State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, China.
Guangdong Provincial Key Laboratory of Virology, Institute of Medical Microbiology, Jinan University, Guangzhou 510632, China.
Viruses. 2020 Dec 30;13(1):47. doi: 10.3390/v13010047.
SARS-CoV-2 is highly pathogenic in humans and poses a great threat to public health worldwide. Clinical data shows a disturbed type I interferon (IFN) response during the virus infection. In this study, we discovered that the nucleocapsid (N) protein of SARS-CoV-2 plays an important role in the inhibition of interferon beta (IFN-β) production. N protein repressed IFN-β production induced by poly(I:C) or upon Sendai virus (SeV) infection. We noted that N protein also suppressed IFN-β production, induced by several signaling molecules downstream of the retinoic acid-inducible gene I (RIG-I) pathway, which is the crucial pattern recognition receptor (PRR) responsible for identifying RNA viruses. Moreover, our data demonstrated that N protein interacted with the RIG-I protein through the DExD/H domain, which has ATPase activity and plays an important role in the binding of immunostimulatory RNAs. These results suggested that SARS-CoV-2 N protein suppresses the IFN-β response through targeting the initial step, potentially the cellular PRR-RNA-recognition step in the innate immune pathway. Therefore, we propose that the SARS-CoV-2 N protein represses IFN-β production by interfering with RIG-I.
严重急性呼吸综合征冠状病毒 2（SARS-CoV-2）在人类中具有高度致病性，对全球公共卫生构成巨大威胁。临床数据显示，病毒感染期间Ⅰ型干扰素（IFN）反应受到干扰。在这项研究中，我们发现 SARS-CoV-2 的核衣壳（N）蛋白在抑制干扰素β（IFN-β）产生方面发挥重要作用。N 蛋白抑制 Poly（I:C）或仙台病毒（SeV）感染诱导的 IFN-β产生。我们注意到，N 蛋白还抑制了几种信号分子诱导的 IFN-β产生，这些信号分子位于 RIG-I 途径的下游，是负责识别 RNA 病毒的关键模式识别受体（PRR）。此外，我们的数据表明，N 蛋白通过具有 ATP 酶活性且在免疫刺激性 RNA 结合中起重要作用的 DExD/H 结构域与 RIG-I 蛋白相互作用。这些结果表明，SARS-CoV-2 N 蛋白通过靶向先天免疫途径中的初始步骤，可能是细胞 PRR-RNA 识别步骤，抑制 IFN-β 反应。因此，我们提出 SARS-CoV-2 N 蛋白通过干扰 RIG-I 抑制 IFN-β 产生。
