Unique and complementary suppression of cGAS-STING and RNA sensing- triggered innate immune responses by SARS-CoV-2 proteins.
Unique and complementary suppression of cGAS-STING and RNA sensing- triggered innate immune responses by SARS-CoV-2 proteins.
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SARS-CoV-2 蛋白对 cGAS-STING 和 RNA 传感触发的先天免疫反应进行独特且互补的抑制
DOI：
10.1038/s41392-021-00515-5
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发表时间：
2021-03-15
影响因子：
39.3
通讯作者：
Yu XF
中科院分区：
文献类型：
--
作者：
Rui Y;Su J;Shen S;Hu Y;Huang D;Zheng W;Lou M;Shi Y;Wang M;Chen S;Zhao N;Dong Q;Cai Y;Xu R;Zheng S;Yu XF
SARS-CoV-2的出现导致了新冠肺炎大流行，导致数百万人感染和数十万人死亡。SARS-CoV-2的有效复制和种群传播表明，它有效地逃避了人类的先天免疫反应，尽管导致这种免疫逃避的病毒蛋白尚不清楚。在这项研究中，我们确定SARS-CoV-2结构蛋白、辅助蛋白和主要的病毒蛋白酶是宿主天然免疫反应的不同途径的有效抑制因子。特别是，主要的病毒蛋白水解酶是RLR和cGAS刺痛途径的有效抑制物。病毒辅助蛋白ORF3a具有独特的抑制刺痛的能力，但不能抑制RLR反应。另一方面，结构蛋白N是一种独特的RLR抑制剂。ORF3a以一种独特的方式结合刺痛并阻断p65的核积聚，从而抑制核因子-κB信号转导。SARS-CoV-2的3CL抑制了STIN的K63-泛素修饰，破坏了STIN功能复合体的组装和下游信号转导。SARS-CoV-2的ORF3a和3CL可以抑制各种脊椎动物的叮咬，包括来自人、小鼠和鸡的叮咬。致病冠状病毒中存在更有效的先天免疫抑制因子，可能会使它们在体内更有效地复制。由于逃避宿主的先天免疫反应对所有病毒的生存至关重要，我们的研究为设计抗SARS-CoV-2的治疗剂提供了见解。
The emergence of SARS-CoV-2 has resulted in the COVID-19 pandemic, leading to millions of infections and hundreds of thousands of human deaths. The efficient replication and population spread of SARS-CoV-2 indicates an effective evasion of human innate immune responses, although the viral proteins responsible for this immune evasion are not clear. In this study, we identified SARS-CoV-2 structural proteins, accessory proteins, and the main viral protease as potent inhibitors of host innate immune responses of distinct pathways. In particular, the main viral protease was a potent inhibitor of both the RLR and cGAS-STING pathways. Viral accessory protein ORF3a had the unique ability to inhibit STING, but not the RLR response. On the other hand, structural protein N was a unique RLR inhibitor. ORF3a bound STING in a unique fashion and blocked the nuclear accumulation of p65 to inhibit nuclear factor-κB signaling. 3CL of SARS-CoV-2 inhibited K63-ubiquitin modification of STING to disrupt the assembly of the STING functional complex and downstream signaling. Diverse vertebrate STINGs, including those from humans, mice, and chickens, could be inhibited by ORF3a and 3CL of SARS-CoV-2. The existence of more effective innate immune suppressors in pathogenic coronaviruses may allow them to replicate more efficiently in vivo. Since evasion of host innate immune responses is essential for the survival of all viruses, our study provides insights into the design of therapeutic agents against SARS-CoV-2.
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影响因子：
158.5
作者：
Li, Qun;Guan, Xuhua;Feng, Zijian
通讯作者：
Feng, Zijian
DOI：
10.1056/nejmoa1312625
发表时间：
2014-08-07
期刊：
The New England journal of medicine
影响因子：
--
作者：
Liu Y;Jesus AA;Marrero B;Yang D;Ramsey SE;Sanchez GAM;Tenbrock K;Wittkowski H;Jones OY;Kuehn HS;Lee CR;DiMattia MA;Cowen EW;Gonzalez B;Palmer I;DiGiovanna JJ;Biancotto A;Kim H;Tsai WL;Trier AM;Huang Y;Stone DL;Hill S;Kim HJ;St Hilaire C;Gurprasad S;Plass N;Chapelle D;Horkayne-Szakaly I;Foell D;Barysenka A;Candotti F;Holland SM;Hughes JD;Mehmet H;Issekutz AC;Raffeld M;McElwee J;Fontana JR;Minniti CP;Moir S;Kastner DL;Gadina M;Steven AC;Wingfield PT;Brooks SR;Rosenzweig SD;Fleisher TA;Deng Z;Boehm M;Paller AS;Goldbach-Mansky R
通讯作者：
Goldbach-Mansky R
ATM 和 IFI16 对 DNA 传感适配器 STING 的非规范激活可在核 DNA 损伤后介导 NF-κB 信号转导。
影响因子：
16
作者：
Dunphy G;Flannery SM;Almine JF;Connolly DJ;Paulus C;Jønsson KL;Jakobsen MR;Nevels MM;Bowie AG;Unterholzner L
通讯作者：
Unterholzner L
影响因子：
29.7
作者：
Brubaker SW;Bonham KS;Zanoni I;Kagan JC
通讯作者：
Kagan JC
影响因子：
56.9
作者：
Anand, K;Ziebuhr, J;Hilgenfeld, R
通讯作者：
Hilgenfeld, R