SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules.
SARS-CoV-2 NSP5 and N protein counteract the RIG-I signaling pathway by suppressing the formation of stress granules.
复制标题
SARS-CoV-2 NSP5 和 N 蛋白通过抑制应激颗粒的形成来抵消 RIG-I 信号通路
DOI：
10.1038/s41392-022-00878-3
复制
发表时间：
2022-01-24
影响因子：
39.3
通讯作者：
Wang PH
中科院分区：
文献类型：
--
作者：
Zheng Y;Deng J;Han L;Zhuang MW;Xu Y;Zhang J;Nan ML;Xiao Y;Zhan P;Liu X;Gao C;Wang PH
作为一种高致病性的人类冠状病毒，SARS-CoV-2必须抵消一个复杂的抗病毒宿主反应网络，以建立感染和传播。核酸诱导的应激反应是抗病毒防御的重要组成部分，与抗病毒天然免疫密切相关。然而，SARS-CoV-2是否调节应激反应途径以实现免疫逃避仍然是一个谜。在这项研究中，SARS-CoV-2 NSP 5和N蛋白被发现减弱抗病毒应激颗粒（avSG）的形成。此外，NSP 5和N抑制由仙台病毒感染或转染dsRNA的合成模拟物poly（I：C）诱导的IFN表达，抑制TBK 1和IRF 3磷酸化，并抑制IRF 3的核转位。此外，异位表达NSP 5或N蛋白的HEK 293 T细胞对水泡性口炎病毒感染的抵抗力较低。在机制上，NSP 5抑制avSG形成并破坏RIG-I-MAVS复合物以减弱RIG-I介导的抗病毒免疫。与NSP 5的多靶点相反，N蛋白特异性靶向RIG-I上游的辅因子。N蛋白与G3 BP 1相互作用以防止avSG形成并保持辅因子G3 BP 1和PACT不激活RIG-I。此外，N蛋白还影响RIG-I对dsRNA的识别。该研究揭示了SARS-CoV-2、应激反应和天然抗病毒免疫之间的密切关系，为COVID-19的致病机制提供了线索。
As a highly pathogenic human coronavirus, SARS-CoV-2 has to counteract an intricate network of antiviral host responses to establish infection and spread. The nucleic acid-induced stress response is an essential component of antiviral defense and is closely related to antiviral innate immunity. However, whether SARS-CoV-2 regulates the stress response pathway to achieve immune evasion remains elusive. In this study, SARS-CoV-2 NSP5 and N protein were found to attenuate antiviral stress granule (avSG) formation. Moreover, NSP5 and N suppressed IFN expression induced by infection of Sendai virus or transfection of a synthetic mimic of dsRNA, poly (I:C), inhibiting TBK1 and IRF3 phosphorylation, and restraining the nuclear translocalization of IRF3. Furthermore, HEK293T cells with ectopic expression of NSP5 or N protein were less resistant to vesicular stomatitis virus infection. Mechanistically, NSP5 suppressed avSG formation and disrupted RIG-I–MAVS complex to attenuate the RIG-I–mediated antiviral immunity. In contrast to the multiple targets of NSP5, the N protein specifically targeted cofactors upstream of RIG-I. The N protein interacted with G3BP1 to prevent avSG formation and to keep the cofactors G3BP1 and PACT from activating RIG-I. Additionally, the N protein also affected the recognition of dsRNA by RIG-I. This study revealed the intimate correlation between SARS-CoV-2, the stress response, and innate antiviral immunity, shedding light on the pathogenic mechanism of COVID-19.
登录
查看更多内容
影响因子：
5.4
作者：
Niemeyer, Daniela;Zillinger, Thomas;Mueller, Marcel A.
通讯作者：
Mueller, Marcel A.
冠状病毒内切核糖核酸酶 nsp15 抑制抗病毒应激颗粒形成，确保病毒有效复制
影响因子：
6.7
作者：
Gao B;Gong X;Fang S;Weng W;Wang H;Chu H;Sun Y;Meng C;Tan L;Song C;Qiu X;Liu W;Forlenza M;Ding C;Liao Y
通讯作者：
Liao Y
影响因子：
5.4
作者：
Hu, Yong;Li, Wei;Cao, Cheng
通讯作者：
Cao, Cheng
影响因子：
3.7
作者：
Onomoto K;Jogi M;Yoo JS;Narita R;Morimoto S;Takemura A;Sambhara S;Kawaguchi A;Osari S;Nagata K;Matsumiya T;Namiki H;Yoneyama M;Fujita T
通讯作者：
Fujita T
影响因子：
13.2
作者：
Moustaqil M;Ollivier E;Chiu HP;Van Tol S;Rudolffi-Soto P;Stevens C;Bhumkar A;Hunter DJB;Freiberg AN;Jacques D;Lee B;Sierecki E;Gambin Y
通讯作者：
Gambin Y