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@ARTICLE{Koch:169874,
      author       = {J. Koch and Z. M. Uckeley and P. Doldan and M. Stanifer and
                      S. Boulant$^*$ and P.-Y. Lozach},
      title        = {{TMPRSS}2 expression dictates the entry route used by
                      {SARS}-{C}o{V}-2 to infect host cells.},
      journal      = {The EMBO journal},
      volume       = {40},
      number       = {16},
      issn         = {1460-2075},
      address      = {Hoboken, NJ [u.a.]},
      publisher    = {Wiley},
      reportid     = {DKFZ-2021-01608},
      pages        = {e107821},
      year         = {2021},
      note         = {2021 Aug 16;40(16):e107821},
      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     = {COVID-19 (Other) / Coronavirus (Other) / SARS-CoV-2 (Other)
                      / protease (Other) / virus entry (Other)},
      cin          = {F140},
      ddc          = {570},
      cid          = {I:(DE-He78)F140-20160331},
      pnm          = {316 - Infektionen, Entzündung und Krebs (POF4-316)},
      pid          = {G:(DE-HGF)POF4-316},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:34159616},
      doi          = {10.15252/embj.2021107821},
      url          = {https://inrepo02.dkfz.de/record/169874},
}