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000169874 0247_ $$2ISSN$$a1460-2075
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000169874 041__ $$aEnglish
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000169874 1001_ $$aKoch, Jana$$b0
000169874 245__ $$aTMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells.
000169874 260__ $$aHoboken, NJ [u.a.]$$bWiley$$c2021
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000169874 500__ $$a2021 Aug 16;40(16):e107821
000169874 520__ $$aSARS-CoV-2 is a newly emerged coronavirus that caused the global COVID-19 outbreak in early 2020. COVID-19 is primarily associated with lung injury, but many other clinical symptoms such as loss of smell and taste demonstrated broad tissue tropism of the virus. Early SARS-CoV-2-host cell interactions and entry mechanisms remain poorly understood. Investigating SARS-CoV-2 infection in tissue culture, we found that the protease TMPRSS2 determines the entry pathway used by the virus. In the presence of TMPRSS2, the proteolytic process of SARS-CoV-2 was completed at the plasma membrane, and the virus rapidly entered the cells within 10 min in a pH-independent manner. When target cells lacked TMPRSS2 expression, the virus was endocytosed and sorted into endolysosomes, from which SARS-CoV-2 entered the cytosol via acid-activated cathepsin L protease 40-60 min post-infection. Overexpression of TMPRSS2 in non-TMPRSS2 expressing cells abolished the dependence of infection on the cathepsin L pathway and restored sensitivity to the TMPRSS2 inhibitors. Together, our results indicate that SARS-CoV-2 infects cells through distinct, mutually exclusive entry routes and highlight the importance of TMPRSS2 for SARS-CoV-2 sorting into either pathway.
000169874 536__ $$0G:(DE-HGF)POF4-316$$a316 - Infektionen, Entzündung und Krebs (POF4-316)$$cPOF4-316$$fPOF IV$$x0
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000169874 650_7 $$2Other$$aCOVID-19
000169874 650_7 $$2Other$$aCoronavirus
000169874 650_7 $$2Other$$aSARS-CoV-2
000169874 650_7 $$2Other$$aprotease
000169874 650_7 $$2Other$$avirus entry
000169874 7001_ $$00000-0001-9770-9873$$aUckeley, Zina M$$b1
000169874 7001_ $$aDoldan, Patricio$$b2
000169874 7001_ $$aStanifer, Megan$$b3
000169874 7001_ $$0P:(DE-He78)4658b59d5b4e54b919fc63ab1213c78f$$aBoulant, Steeve$$b4$$udkfz
000169874 7001_ $$00000-0002-9966-1452$$aLozach, Pierre-Yves$$b5
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