Key Laboratory of Special Pathogens and Biosafety, Center for Biosafety Mega-Science, Wuhan Institute of Virology, Chinese Academy of Sciences, 430071, Wuhan, China.
University of Chinese Academy of Sciences, 100049, Beijing, China.
Cell Mol Immunol. 2021 Mar;18(3):613-620. doi: 10.1038/s41423-020-00571-x. Epub 2020 Oct 27.
A novel SARS-related coronavirus (SARS-CoV-2) has recently emerged as a serious pathogen that causes high morbidity and substantial mortality. However, the mechanisms by which SARS-CoV-2 evades host immunity remain poorly understood. Here, we identified SARS-CoV-2 membrane glycoprotein M as a negative regulator of the innate immune response. We found that the M protein interacted with the central adaptor protein MAVS in the innate immune response pathways. This interaction impaired MAVS aggregation and its recruitment of downstream TRAF3, TBK1, and IRF3, leading to attenuation of the innate antiviral response. Our findings reveal a mechanism by which SARS-CoV-2 evades the innate immune response and suggest that the M protein of SARS-CoV-2 is a potential target for the development of SARS-CoV-2 interventions.
一种新型的严重急性呼吸综合征相关冠状病毒（SARS-CoV-2）最近出现，成为一种严重的病原体，导致高发病率和大量死亡。然而，SARS-CoV-2 逃避宿主免疫的机制仍知之甚少。在这里，我们确定 SARS-CoV-2 膜糖蛋白 M 是先天免疫反应的负调节剂。我们发现 M 蛋白与先天免疫反应途径中的中央衔接蛋白 MAVS 相互作用。这种相互作用削弱了 MAVS 的聚集及其募集下游的 TRAF3、TBK1 和 IRF3，导致先天抗病毒反应减弱。我们的研究结果揭示了 SARS-CoV-2 逃避先天免疫反应的一种机制，并表明 SARS-CoV-2 的 M 蛋白是开发 SARS-CoV-2 干预措施的潜在靶点。
