| Title | SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage |
| Authors | Ma, Juan Zhu, Fangrui Zhao, Min Shao, Fei Yu, Dou Ma, Jiangwen Zhang, Xusheng Li, Weitao Qian, Yan Zhang, Yan Jiang, Dong Wang, Shuo Xia, Pengyan |
| Affiliation | Peking Univ, Sch Basic Med Sci, Dept Immunol, Beijing, Peoples R China Peking Univ, NHC Key Lab Med Immunol, Beijing, Peoples R China Chinese Acad Med Sci, Key Lab Mol Immunol, Beijing, Peoples R China Chinese Acad Sci, Inst Microbiol, CAS Key Lab Pathogen Microbiol & Immunol, Beijing, Peoples R China Chinese Acad Sci, Ctr Biosafety Megasci, Wuhan, Peoples R China Peking Univ Third Hosp, Dept Sports Med, Beijing, Peoples R China Peking Univ, Beijing Key Lab Sports Injuries, Inst Sports Med, Beijing, Peoples R China |
| Keywords | MECHANISM GSDMD CASPASE-11 ACTIVATION IMMUNITY |
| Issue Date | Aug-2021 |
| Publisher | EMBO JOURNAL |
| Abstract | 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. |
| URI | http://hdl.handle.net/20.500.11897/619583 |
| ISSN | 0261-4189 |
| DOI | 10.15252/embj.2021108249 |
| Indexed | SCI(E) |
| Appears in Collections: | 基础医学院 第三医院 |
