Phase-separated nucleocapsid protein of SARS-CoV-2 suppresses cGAS-DNA recognition by disrupting cGAS-G3BP1 complex
作者机构：Guangdong Province Key Laboratory of Pharmaceutical Functional GenesThe First Affiliated Hospital of Sun Yat-sen UniversitySchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdongChina MOE Key Laboratory of Gene Function and RegulationState Key Laboratory of BiocontrolSchool of Life SciencesSun Yat-sen UniversityGuangzhouGuangdongChina State Key Laboratory of Respiratory DiseaseGuangzhou Institute of Respiratory DiseaseThe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhouGuangdongChina Department of Critical Care MedicineThe First Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdongChina
出 版 物：《Signal Transduction and Targeted Therapy》 (信号转导与靶向治疗（英文）)
年 卷 期：2023年第8卷第5期
页 面：2392-2407页
核心收录：
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
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)
主 题：interferon separated cGAS
摘 要：Currently,the incidence and fatality rate of SARS-CoV-2 remain continually high ***-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 *** progresses have been made in revealing the multiple strategies employed by SARS-CoV-2 in impairing canonical RNA sensing ***,it remains to be determined about the SARS-CoV-2 antagonism of cGAS-mediated activation of IFN responses during *** 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 *** countermeasures,SARS-CoV-2 nucleocapsid(N)protein restricts the DNA recognition capacity of cGAS to impair cGAS-induced IFN-I ***,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 *** 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.
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