TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells
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 in...
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| Hauptverfasser: | , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
13 July 2021
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| In: |
The EMBO journal
Year: 2021, Jahrgang: 40, Heft: 16, Pages: 1-20 |
| ISSN: | 1460-2075 |
| DOI: | 10.15252/embj.2021107821 |
| Online-Zugang: | Verlag, kostenfrei, Volltext: https://doi.org/10.15252/embj.2021107821 Verlag, kostenfrei, Volltext: https://www.embopress.org/doi/full/10.15252/embj.2021107821 
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| Verfasserangaben: | Jana Koch, Zina M Uckeley, Patricio Doldan, Megan Stanifer, Steeve Boulant & Pierre-Yves Lozach |
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| 520 | |a 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. | ||
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