tetano
Editor, Senior Moderator
EMBO J
. 2021 Jul 22;e108249.
doi: 10.15252/embj.2021108249. Online ahead of print.
SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage
Juan Ma[SUP] 1 2 3 [/SUP], Fangrui Zhu[SUP] 1 2 3 [/SUP], Min Zhao[SUP] 4 5 [/SUP], Fei Shao[SUP] 4 5 [/SUP], Dou Yu[SUP] 4 5 [/SUP], Jiangwen Ma[SUP] 4 5 [/SUP], Xusheng Zhang[SUP] 4 5 [/SUP], Weitao Li[SUP] 1 2 3 [/SUP], Yan Qian[SUP] 1 2 3 [/SUP], Yan Zhang[SUP] 1 2 3 [/SUP], Dong Jiang[SUP] 6 7 [/SUP], Shuo Wang[SUP] 4 5 [/SUP], Pengyan Xia[SUP] 1 2 3 [/SUP]
Affiliations
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 1b (IL-1b) expression, but reduced IL-1b 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.
Keywords: GSDMD; SARS-CoV-2; inflammasome; nucleocapsid; pyroptosis.
. 2021 Jul 22;e108249.
doi: 10.15252/embj.2021108249. Online ahead of print.
SARS-CoV-2 nucleocapsid suppresses host pyroptosis by blocking Gasdermin D cleavage
Juan Ma[SUP] 1 2 3 [/SUP], Fangrui Zhu[SUP] 1 2 3 [/SUP], Min Zhao[SUP] 4 5 [/SUP], Fei Shao[SUP] 4 5 [/SUP], Dou Yu[SUP] 4 5 [/SUP], Jiangwen Ma[SUP] 4 5 [/SUP], Xusheng Zhang[SUP] 4 5 [/SUP], Weitao Li[SUP] 1 2 3 [/SUP], Yan Qian[SUP] 1 2 3 [/SUP], Yan Zhang[SUP] 1 2 3 [/SUP], Dong Jiang[SUP] 6 7 [/SUP], Shuo Wang[SUP] 4 5 [/SUP], Pengyan Xia[SUP] 1 2 3 [/SUP]
Affiliations
- PMID: 34296442
- DOI: 10.15252/embj.2021108249
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 1b (IL-1b) expression, but reduced IL-1b 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.
Keywords: GSDMD; SARS-CoV-2; inflammasome; nucleocapsid; pyroptosis.