tetano
Editor, Senior Moderator
J Biol Chem
. 2021 Jan 18;100306.
doi: 10.1016/j.jbc.2021.100306. Online ahead of print.
SARS-CoV-2 infects cells following viral entry via clathrin-mediated endocytosis
Armin Bayati[SUP] 1 [/SUP], Rahul Kumar[SUP] 1 [/SUP], Vincent Francis[SUP] 1 [/SUP], Peter S McPherson[SUP] 2 [/SUP]
Affiliations
Abstract
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 following 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.
Keywords: COVID-19; SARS-CoV-2; clathrin; dynamin; endocytosis; infection; virus entry.
. 2021 Jan 18;100306.
doi: 10.1016/j.jbc.2021.100306. Online ahead of print.
SARS-CoV-2 infects cells following viral entry via clathrin-mediated endocytosis
Armin Bayati[SUP] 1 [/SUP], Rahul Kumar[SUP] 1 [/SUP], Vincent Francis[SUP] 1 [/SUP], Peter S McPherson[SUP] 2 [/SUP]
Affiliations
- PMID: 33476648
- DOI: 10.1016/j.jbc.2021.100306
Abstract
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 following 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.
Keywords: COVID-19; SARS-CoV-2; clathrin; dynamin; endocytosis; infection; virus entry.