冠状病毒NP通过G3BP蛋白调控宿主抗病毒免疫的机制研究

核衣壳蛋白（NP）是冠状病毒组装的关键蛋白。作为主要致病因子，NP能够抑制宿主先天性免疫，但具体机制不清。宿主G3BP可以通过压力小体（SG）、RIG-I以及cGAS信号通路广泛参与宿主抗病毒反应。前期工作发现，新型冠状病毒NP与G3BP蛋白存在相互作用（KD<0.1μM）。NP可抑制G3BP依赖的SG形成，同时抑制G3BP依赖的干扰素相关基因的表达。因此，我们推测冠状病毒NP通过与宿主G3BP结合，一方面抑制抗病毒压力小体的形成，另一方面抑制RIG-I调控的干扰素途径，以及调控炎症小体介导的炎症反应。上述功能可抑制机体的抗病毒效应，促进病毒复制，加重病毒感染后导致的炎症反应。本课题拟通过实毒感染模型进一步解析冠状病毒NP通过G3BP调控宿主抗病毒免疫的机制，阐明不同冠状病毒NP与G3BP相互作用强弱与其致病性的关系，为NP作为治疗靶点提供理论依据，为新冠疫情防治提供新思路和新方法。

The nucleocapsid protein (NP) of coronavirus serve central roles in the viral genome packaging and the antagonism of the host innate immunity. G3BPs take charge of host anti-viral immune responses by promoting SG formation and activating RIG-I- or cGAS- involved viral recognition and cytokines release. We found that NPSARS-CoV-2 binds to G3BPs with high binding affinities (KD<0.1μM). Moreover, NP antagonize G3BPs-dependent SG formation and interferon production. We propose that NPSARS-CoV-2 may abolish G3BPs-involved SG assemble, RIG-I activation and inflammation, which dampen the innate immunity and promote virus replication. Further investigation with live virus infection into the mechanism behind its high pathogenicity and the G3BP-involved host anti-viral response regulated by NP may contribute to the growing body of knowledge regarding the pathogenicity of NP and provide insight into the new therapeutics that target the NP.