Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex  

作　　者：Sihui Cai Chenqiu Zhang Zhen Zhuang Shengnan Zhang Ling Ma Shuai Yang Tao Zhou Zheyu Wang Weihong Xie Shouheng Jin Jincun Zhao Xiangdong Guan Jianfeng Wu Jun Cui Yaoxing Wu 

机构地区：[1]Guangdong Province Key Laboratory of Pharmaceutical Functional Genes,The First Affiliated Hospital of Sun Yat-sen University,School of Life Sciences,Sun Yat-sen University,Guangzhou,Guangdong,China [2]MOE Key Laboratory of Gene Function and Regulation,State Key Laboratory of Biocontrol,School of Life Sciences,Sun Yat-sen University,Guangzhou,Guangdong,China [3]State Key Laboratory of Respiratory Disease,Guangzhou Institute of Respiratory Disease,The First Affiliated Hospital of Guangzhou Medical University,Guangzhou,Guangdong,China [4]Department of Critical Care Medicine,The First Affiliated Hospital of Sun Yat-sen University,Guangzhou,Guangdong,China

出　　处：《Signal Transduction and Targeted Therapy》2023年第5期2392-2407,共16页信号转导与靶向治疗（英文）

基　　金：supported by the National Key R&D Program of China (2020YFA0908700);Guangdong Provincial Key R&D Program for Covid 19 (232020012620600001);National Natural Science Foundation of China (82025001,31970700,32170876);Guangdong Basic and Applied Basic Research Foundation (2020B1515120090);Natural Science Foundation of Guangdong Province,China (2021A1515012179);Guangdong Clinical Research Center for Critical Care Medicine (2020B1111170005);the Sun Yat‑sen University Clinical Research Program 5010 (2019002).

摘　　要：Currently,the incidence and fatality rate of SARS-CoV-2 remain continually high worldwide.COVID-19 patients infected with SARS-CoV-2 exhibited decreased type I interferon(IFN-I)signal,along with limited activation of antiviral immune responses as well as enhanced viral infectivity.Dramatic progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing pathways.However,it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during infection.In the current study,we figure out that SARS-CoV-2 infection leads to the accumulation of released mitochondria DNA(mtDNA),which in turn triggers cGAS to activate IFN-I signaling.As countermeasures,SARS-CoV-2 nucleocapsid(N)protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I signaling.Mechanically,N protein disrupts the assembly of cGAS with its co-factor G3BP1 by undergoing DNA-induced liquid-liquid phase separation(LLPS),subsequently impairs the double-strand DNA(dsDNA)detection ability of cGAS.Taken together,our findings unravel a novel antagonistic strategy by which SARS-CoV-2 reduces DNA-triggered IFN-I pathway through interfering with cGAS-DNA phase separation.

关 键 词：INTERFERON SEPARATED cGAS 

分 类 号：R563.1[医药卫生—呼吸系统]