%0 Journal Article
%A Koch, Jana
%A Uckeley, Zina M
%A Doldan, Patricio
%A Stanifer, Megan
%A Boulant, Steeve
%A Lozach, Pierre-Yves
%T TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells.
%J The EMBO journal
%V 40
%N 16
%@ 1460-2075
%C Hoboken, NJ [u.a.]
%I Wiley
%M DKFZ-2021-01608
%P e107821
%D 2021
%Z 2021 Aug 16;40(16):e107821
%X 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.
%K COVID-19 (Other)
%K Coronavirus (Other)
%K SARS-CoV-2 (Other)
%K protease (Other)
%K virus entry (Other)
%F PUB:(DE-HGF)16
%9 Journal Article
%$ pmid:34159616
%R 10.15252/embj.2021107821
%U https://inrepo02.dkfz.de/record/169874