SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis.

Content Provider	Europe PMC
Author	Bayati, Armin Kumar, Rahul Francis, Vincent McPherson, Peter S.
Copyright Year	2021
Abstract	Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of COVID-19, so understanding its biology and infection mechanisms is critical to facing this major medical challenge. SARS-CoV-2 is known to use its spike glycoprotein to interact with the cell surface as a first step in the infection process. As for other coronaviruses, it is likely that SARS-CoV-2 next undergoes endocytosis, but whether or not this is required for infectivity and the precise endocytic mechanism used are unknown. Using purified spike glycoprotein and lentivirus pseudotyped with spike glycoprotein, a common model of SARS-CoV-2 infectivity, we now demonstrate that after engagement with the plasma membrane, SARS-CoV-2 undergoes rapid, clathrin-mediated endocytosis. This suggests that transfer of viral RNA to the cell cytosol occurs from the lumen of the endosomal system. Importantly, we further demonstrate that knockdown of clathrin heavy chain, which blocks clathrin-mediated endocytosis, reduces viral infectivity. These discoveries reveal that SARS-CoV-2 uses clathrin-mediated endocytosis to gain access into cells and suggests that this process is a key aspect of virus infectivity.
ISSN	00219258
Volume Number	296
PubMed Central reference number	PMC7816624
PubMed reference number	33476648
Journal	The Journal of Biological Chemistry [J. Biol. Chem]
e-ISSN	1083351X
DOI	10.1016/j.jbc.2021.100306
Language	English
Publisher	American Society for Biochemistry and Molecular Biology
Publisher Date	2021-01-19
Access Restriction	Open
Rights License	This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/). © 2021 The Authors
Subject Keyword	clathrin COVID-19 dynamin endocytosis infection SARS-CoV-2 virus entry ACE2, angiotensin-converting enzyme 2 CHC, clathrin heavy chain CQ, chloroquine MERS-CoV, Middle-East respiratory syndrome coronavirus SARS-CoV, severe acute respiratory syndrome coronavirus SARS-CoV-2, severe acute respiratory syndrome coronavirus 2 Tf, transferrin TfR, Tf receptor
Content Type	Text
Resource Type	Article
Subject	Cell Biology Molecular Biology Biochemistry