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SARS-CoV-2 infects cells after viral entry via clathrin-mediated endocytosis
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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.
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“Interfering expression of clathrin heavy chain in HEK293 (stably expressing ACE2), limits SARS-CoV-2 viral infectivity [66].”
From Insights of Endocytosis Signaling in Health and Disease (2023) · cites this paper as [66]
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Metadata
- Authors
- Bayati, A., Kumar, R., Francis, V., & McPherson, P. S.
- Affiliations
- Montreal Neurological Institute and Hospital (CA)
- Corresponding author
- McPherson, Peter S.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2021-01
- Volume
- 296
- Pages
- 100306
- ISSN
- 0021-9258 (ISSN-L)
- PMC
- PMC7816624
- OpenAlex
- W3121790907
- Cited by
- 499
- References
- 55
- Citations by year
- 2026: 28 · 2025: 53 · 2024: 87 · 2023: 106 · 2022: 150 · 2021: 70
- FWCI
- 32.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- Natural Sciences and Engineering Research Council of Canada
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 detection and testing
- Keywords
- SARS-CoV-2, clathrin-mediated endocytosis, viral entry, spike protein, clathrin heavy chain, endosomal escape, COVID-19 pandemic, infection mechanism
- MeSH terms
- A549 Cells, Angiotensin-Converting Enzyme 2, SARS-CoV-2, Animals, Chlorocebus aethiops, Endocytosis, Gene Expression Regulation, Genetic Vectors, Humans, Hydrazones, Protein Binding, Endosomes, Sulfonamides, Vero Cells, Signal Transduction, Lentivirus, Clathrin Heavy Chains, RNA, Small Interfering, Virus Internalization, Thiazolidines, Host-Pathogen Interactions, HEK293 Cells, Spike Glycoprotein, Coronavirus
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