TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells

• Verfasst von: Koch, Jana [VerfasserIn]
• Verfasst von: Uckeley, Zina Maria [VerfasserIn]
• Verfasst von: Doldan, Patricio [VerfasserIn]
• Verfasst von: Stanifer, Megan [VerfasserIn]
• Verfasst von: Boulant, Steeve [VerfasserIn]
• Verfasst von: Lozach, Pierre-Yves [VerfasserIn]
• Titel: TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells
• Verf.angabe: Jana Koch, Zina M Uckeley, Patricio Doldan, Megan Stanifer, Steeve Boulant & Pierre-Yves Lozach
• E-Jahr: 2021
• Jahr: 13 July 2021
• Umfang: 20 S.
• Illustrationen: Illustrationen
• Fussnoten: Gesehen am 17.08.2023
• Titel Quelle: Enthalten in: European Molecular Biology OrganizationThe EMBO journal
• Ort Quelle: Heidelberg : EMBO Press, 1982
• Jahr Quelle: 2021
• Band/Heft Quelle: 40(2021), 16, Artikel-ID e107821, Seite 1-20
• ISSN Quelle: 1460-2075
• DOI: doi:10.15252/embj.2021107821
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Coronavirus
• Sach-SW: COVID-19
• Sach-SW: protease
• Sach-SW: SARS-CoV-2
• Sach-SW: virus entry
• K10plus-PPN: 1856419231
• K10plus-PPN:
  Universitätsbibliothek
• Lokale URL UB: Zum Volltext

Abstract

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.