Efficient activation of the severe acute respiratory syndrome coronavirus spike protein by the transmembrane protease TMPRSS2

Journal of Virology
Shutoku MatsuyamaFumihiro Taguchi

Abstract

The distribution of the severe acute respiratory syndrome coronavirus (SARS-CoV) receptor, an angiotensin-converting enzyme 2 (ACE2), does not strictly correlate with SARS-CoV cell tropism in lungs; therefore, other cellular factors have been predicted to be required for activation of virus infection. In the present study, we identified transmembrane protease serine 2 (TMPRSS2), whose expression does correlate with SARS-CoV infection in the upper lobe of the lung. In Vero cells expressing TMPRSS2, large syncytia were induced by SARS-CoV infection. Further, the lysosome-tropic reagents failed to inhibit, whereas the heptad repeat peptide efficiently inhibited viral entry into cells, suggesting that TMPRSS2 affects the S protein at the cell surface and induces virus-plasma membrane fusion. On the other hand, production of virus in TMPRSS2-expressing cells did not result in S-protein cleavage or increased infectivity of the resulting virus. Thus, TMPRSS2 affects the entry of virus but not other phases of virus replication. We hypothesized that the spatial orientation of TMPRSS2 vis-a-vis S protein is a key mechanism underling this phenomenon. To test this, the TMPRSS2 and S proteins were expressed in cells labeled with fluorescent...Continue Reading

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Citations

May 27, 2011·Journal of Virology·Kazuya ShiratoFumihiro Taguchi
Dec 14, 2012·PLoS Neglected Tropical Diseases·Andrea MarziHeinz Feldmann
Dec 19, 2013·PLoS Pathogens·Bastian HatesuerKlaus Schughart
Oct 7, 2011·Uirusu·Shutoku Matsuyama
Mar 24, 2012·Current Opinion in Virology·Denis Gerlier
Sep 10, 2014·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Mariko EsumiTakaji Wakita
May 10, 2011·Free Radical Biology & Medicine·Matthew J KesicIlona Jaspers
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Jun 10, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Erzsebet Pászti-GereTorsten Steinmetzer
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jung-Eun ParkTom Gallagher
Dec 22, 2016·Expert Opinion on Therapeutic Patents·Yu-Yao LiGui-Zhen Ao
May 17, 2012·Viruses·Taylor Heald-Sargent, Tom Gallagher
Aug 24, 2013·Journal of Virology·Masako AbeMakoto Takeda
Mar 27, 2015·Clinical Microbiology Reviews·Jasper F W ChanKwok-Yung Yuen
Aug 15, 2014·Journal of Virology·Pawel ZmoraStephanie Bertram

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