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| Home > Publications database > TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells. > print |
| 001 | 169874 | ||
| 005 | 20240229133658.0 | ||
| 024 | 7 | _ | |a 10.15252/embj.2021107821 |2 doi |
| 024 | 7 | _ | |a pmid:34159616 |2 pmid |
| 024 | 7 | _ | |a 0261-4189 |2 ISSN |
| 024 | 7 | _ | |a 1460-2075 |2 ISSN |
| 024 | 7 | _ | |a altmetric:108084434 |2 altmetric |
| 037 | _ | _ | |a DKFZ-2021-01608 |
| 041 | _ | _ | |a English |
| 082 | _ | _ | |a 570 |
| 100 | 1 | _ | |a Koch, Jana |b 0 |
| 245 | _ | _ | |a TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells. |
| 260 | _ | _ | |a Hoboken, NJ [u.a.] |c 2021 |b Wiley |
| 336 | 7 | _ | |a article |2 DRIVER |
| 336 | 7 | _ | |a Output Types/Journal article |2 DataCite |
| 336 | 7 | _ | |a Journal Article |b journal |m journal |0 PUB:(DE-HGF)16 |s 1642169139_14743 |2 PUB:(DE-HGF) |
| 336 | 7 | _ | |a ARTICLE |2 BibTeX |
| 336 | 7 | _ | |a JOURNAL_ARTICLE |2 ORCID |
| 336 | 7 | _ | |a Journal Article |0 0 |2 EndNote |
| 500 | _ | _ | |a 2021 Aug 16;40(16):e107821 |
| 520 | _ | _ | |a 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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| 588 | _ | _ | |a Dataset connected to CrossRef, PubMed, , Journals: inrepo01.inet.dkfz-heidelberg.de |
| 650 | _ | 7 | |a COVID-19 |2 Other |
| 650 | _ | 7 | |a Coronavirus |2 Other |
| 650 | _ | 7 | |a SARS-CoV-2 |2 Other |
| 650 | _ | 7 | |a protease |2 Other |
| 650 | _ | 7 | |a virus entry |2 Other |
| 700 | 1 | _ | |a Uckeley, Zina M |0 0000-0001-9770-9873 |b 1 |
| 700 | 1 | _ | |a Doldan, Patricio |b 2 |
| 700 | 1 | _ | |a Stanifer, Megan |b 3 |
| 700 | 1 | _ | |a Boulant, Steeve |0 P:(DE-He78)4658b59d5b4e54b919fc63ab1213c78f |b 4 |u dkfz |
| 700 | 1 | _ | |a Lozach, Pierre-Yves |0 0000-0002-9966-1452 |b 5 |
| 773 | _ | _ | |a 10.15252/embj.2021107821 |0 PERI:(DE-600)1467419-1 |n 16 |p e107821 |t The EMBO journal |v 40 |y 2021 |x 1460-2075 |
| 909 | C | O | |p VDB |o oai:inrepo02.dkfz.de:169874 |
| 910 | 1 | _ | |a Deutsches Krebsforschungszentrum |0 I:(DE-588b)2036810-0 |k DKFZ |b 4 |6 P:(DE-He78)4658b59d5b4e54b919fc63ab1213c78f |
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| 913 | 0 | _ | |a DE-HGF |b Gesundheit |l Krebsforschung |1 G:(DE-HGF)POF3-310 |0 G:(DE-HGF)POF3-316 |3 G:(DE-HGF)POF3 |2 G:(DE-HGF)POF3-300 |4 G:(DE-HGF)POF |v Infections and cancer |x 0 |
| 914 | 1 | _ | |y 2021 |
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