SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage

被引：95

作者：

Ma, Juan ^{[1
,2
,3
]}

Zhu, Fangrui ^{[1
,2
,3
]}

Zhao, Min ^{[4
,5
]}

Shao, Fei ^{[4
,5
]}

Yu, Dou ^{[4
,5
]}

Ma, Jiangwen ^{[4
,5
]}

Zhang, Xusheng ^{[4
,5
]}

Li, Weitao ^{[1
,2
,3
]}

Qian, Yan ^{[1
,2
,3
]}

Zhang, Yan ^{[1
,2
,3
]}

Jiang, Dong ^{[6
,7
]}

Wang, Shuo ^{[4
,5
]}

Xia, Pengyan ^{[1
,2
,3
]}

机构：

[1] Peking Univ, Sch Basic Med Sci, Dept Immunol, Beijing, Peoples R China

[2] Peking Univ, NHC Key Lab Med Immunol, Beijing, Peoples R China

[3] Chinese Acad Med Sci, Key Lab Mol Immunol, Beijing, Peoples R China

[4] Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China

[5] Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan, Peoples R China

[6] Peking Univ Third Hosp, Dept Sports Med, Beijing, Peoples R China

[7] Peking Univ, Beijing Key Lab Sports Injuries, Inst Sports Med, Beijing, Peoples R China

来源：

EMBO JOURNAL | 2021年 / 40卷 / 18期

基金：

国家重点研发计划; 中国国家自然科学基金;

关键词：

GSDMD; inflammasome; nucleocapsid; pyroptosis; SARS-CoV-2; MECHANISM; GSDMD; CASPASE-11; ACTIVATION; IMMUNITY; DISEASE;

D O I：

10.15252/embj.2021108249

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

SARS-CoV-2 is an emerging coronavirus that causes dysfunctions in multiple human cells and tissues. Studies have looked at the entry of SARS-CoV-2 into host cells mediated by the viral spike protein and human receptor ACE2. However, less is known about the cellular immune responses triggered by SARS-CoV-2 viral proteins. Here, we show that the nucleocapsid of SARS-CoV-2 inhibits host pyroptosis by blocking Gasdermin D (GSDMD) cleavage. SARS-CoV-2-infected monocytes show enhanced cellular interleukin-1 beta (IL-1 beta) expression, but reduced IL-1 beta secretion. While SARS-CoV-2 infection promotes activation of the NLRP3 inflammasome and caspase-1, GSDMD cleavage and pyroptosis are inhibited in infected human monocytes. SARS-CoV-2 nucleocapsid protein associates with GSDMD in cells and inhibits GSDMD cleavage in vitro and in vivo. The nucleocapsid binds the GSDMD linker region and hinders GSDMD processing by caspase-1. These insights into how SARS-CoV-2 antagonizes cellular inflammatory responses may open new avenues for treating COVID-19 in the future.

引用

页数：17

共 49 条

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