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SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis.
- Source :
-
The Journal of biological chemistry [J Biol Chem] 2021 Jan-Jun; Vol. 296, pp. 100306. Date of Electronic Publication: 2021 Jan 19. - Publication 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.<br />Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.<br /> (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- A549 Cells
Angiotensin-Converting Enzyme 2 metabolism
Animals
Chlorocebus aethiops
Clathrin Heavy Chains antagonists & inhibitors
Clathrin Heavy Chains metabolism
Endocytosis drug effects
Endosomes drug effects
Endosomes metabolism
Endosomes virology
Gene Expression Regulation
Genetic Vectors chemistry
Genetic Vectors metabolism
HEK293 Cells
Host-Pathogen Interactions genetics
Humans
Hydrazones pharmacology
Lentivirus genetics
Lentivirus metabolism
Protein Binding drug effects
RNA, Small Interfering genetics
RNA, Small Interfering metabolism
SARS-CoV-2 drug effects
SARS-CoV-2 metabolism
Signal Transduction
Spike Glycoprotein, Coronavirus metabolism
Sulfonamides pharmacology
Thiazolidines pharmacology
Vero Cells
Angiotensin-Converting Enzyme 2 genetics
Clathrin Heavy Chains genetics
Endocytosis genetics
SARS-CoV-2 genetics
Spike Glycoprotein, Coronavirus genetics
Virus Internalization drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1083-351X
- Volume :
- 296
- Database :
- MEDLINE
- Journal :
- The Journal of biological chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 33476648
- Full Text :
- https://doi.org/10.1016/j.jbc.2021.100306