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SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage.
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.
  • Ma J; Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
  • Zhu F; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China.
  • Zhao M; Key Laboratory of Molecular Immunology, Chinese Academy of Medical Sciences, Beijing, China.
  • Shao F; Department of Immunology, School of Basic Medical Sciences, Peking University, Beijing, China.
  • Yu D; NHC Key Laboratory of Medical Immunology, Peking University, Beijing, China.
  • Ma J; Key Laboratory of Molecular Immunology, Chinese Academy of Medical Sciences, Beijing, China.
  • Zhang X; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Li W; Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Qian Y; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Zhang Y; Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Jiang D; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
  • Wang S; Center for Biosafety Mega-Science, Chinese Academy of Sciences, Wuhan, China.
  • Xia P; CAS Key Laboratory of Pathogenic Microbiology and Immunology, Institute of Microbiology, Chinese Academy of Sciences, Beijing, China.
EMBO J ; 40(18): e108249, 2021 09 15.
Article in English | MEDLINE | ID: covidwho-1323479
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-1ß (IL-1ß) expression, but reduced IL-1ß 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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Nucleocapsid / Phosphate-Binding Proteins / Intracellular Signaling Peptides and Proteins / Pyroptosis / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: EMBO J Year: 2021 Document Type: Article Affiliation country: Embj.2021108249

Full text: Available Collection: International databases Database: MEDLINE Main subject: Nucleocapsid / Phosphate-Binding Proteins / Intracellular Signaling Peptides and Proteins / Pyroptosis / SARS-CoV-2 / COVID-19 Limits: Animals / Humans Language: English Journal: EMBO J Year: 2021 Document Type: Article Affiliation country: Embj.2021108249