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

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? (IL-1?) expression, but reduced IL-1? 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.
Mesh Terms:
Angiotensin-Converting Enzyme 2, Animals, COVID-19, Caspase 1, HEK293 Cells, Host-Pathogen Interactions, Humans, Inflammasomes, Interleukin-1beta, Intracellular Signaling Peptides and Proteins, Mice, Monocytes, NLR Family, Pyrin Domain-Containing 3 Protein, Nucleocapsid, Phosphate-Binding Proteins, Pyroptosis, SARS-CoV-2, Spike Glycoprotein, Coronavirus, THP-1 Cells
EMBO J
Date: Sep. 15, 2021
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