TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells.
EMBO J
; 40(16): e107821, 2021 08 16.
Article
in English
| MEDLINE | ID: covidwho-1280957
ABSTRACT
SARS-CoV-2 is a newly emerged coronavirus that caused the global COVID-19 outbreak in early 2020. COVID-19 is primarily associated with lung injury, but many other clinical symptoms such as loss of smell and taste demonstrated broad tissue tropism of the virus. Early SARS-CoV-2-host cell interactions and entry mechanisms remain poorly understood. Investigating SARS-CoV-2 infection in tissue culture, we found that the protease TMPRSS2 determines the entry pathway used by the virus. In the presence of TMPRSS2, the proteolytic process of SARS-CoV-2 was completed at the plasma membrane, and the virus rapidly entered the cells within 10 min in a pH-independent manner. When target cells lacked TMPRSS2 expression, the virus was endocytosed and sorted into endolysosomes, from which SARS-CoV-2 entered the cytosol via acid-activated cathepsin L protease 40-60 min post-infection. Overexpression of TMPRSS2 in non-TMPRSS2 expressing cells abolished the dependence of infection on the cathepsin L pathway and restored sensitivity to the TMPRSS2 inhibitors. Together, our results indicate that SARS-CoV-2 infects cells through distinct, mutually exclusive entry routes and highlight the importance of TMPRSS2 for SARS-CoV-2 sorting into either pathway.
Keywords
Full text:
Available
Collection:
International databases
Database:
MEDLINE
Main subject:
Serine Endopeptidases
/
Cathepsin L
/
SARS-CoV-2
/
COVID-19
Type of study:
Prognostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
EMBO J
Year:
2021
Document Type:
Article
Affiliation country:
Embj.2021107821
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