SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis.
A549 Cells
Angiotensin-Converting Enzyme 2
/ genetics
Animals
Chlorocebus aethiops
Clathrin Heavy Chains
/ antagonists & inhibitors
Endocytosis
/ drug effects
Endosomes
/ drug effects
Gene Expression Regulation
Genetic Vectors
/ chemistry
HEK293 Cells
Host-Pathogen Interactions
/ genetics
Humans
Hydrazones
/ pharmacology
Lentivirus
/ genetics
Protein Binding
/ drug effects
RNA, Small Interfering
/ genetics
SARS-CoV-2
/ drug effects
Signal Transduction
Spike Glycoprotein, Coronavirus
/ genetics
Sulfonamides
/ pharmacology
Thiazolidines
/ pharmacology
Vero Cells
Virus Internalization
/ drug effects
COVID-19
SARS-CoV-2
clathrin
dynamin
endocytosis
infection
virus entry
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
Historique:
received:
11
11
2020
revised:
06
01
2021
accepted:
15
01
2021
pubmed:
22
1
2021
medline:
14
7
2021
entrez:
21
1
2021
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 33476648
pii: S0021-9258(21)00075-2
doi: 10.1016/j.jbc.2021.100306
pmc: PMC7816624
pii:
doi:
Substances chimiques
CLTC protein, human
0
Hydrazones
0
N'-(3,4-dihydroxybenzylidene)-3-hydroxy-2-naphthahydrazide
0
RNA, Small Interfering
0
Spike Glycoprotein, Coronavirus
0
Sulfonamides
0
Thiazolidines
0
pitstop 2
0
spike protein, SARS-CoV-2
0
Clathrin Heavy Chains
114899-12-6
ACE2 protein, human
EC 3.4.17.23
Angiotensin-Converting Enzyme 2
EC 3.4.17.23
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
100306Informations de copyright
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article.
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