Inhibition of proprotein convertases abrogates processing of the middle eastern respiratory syndrome coronavirus spike protein in infected cells but does not reduce viral infectivity

The Journal of Infectious Diseases
Stefanie GiererStefan Pöhlmann

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) infection is associated with a high case-fatality rate, and the potential pandemic spread of the virus is a public health concern. The spike protein of MERS-CoV (MERS-S) facilitates viral entry into host cells, which depends on activation of MERS-S by cellular proteases. Proteolytic activation of MERS-S during viral uptake into target cells has been demonstrated. However, it is unclear whether MERS-S is also cleaved during S protein synthesis in infected cells and whether cleavage is required for MERS-CoV infectivity. Here, we show that MERS-S is processed by proprotein convertases in MERS-S-transfected and MERS-CoV-infected cells and that several RXXR motifs located at the border between the surface and transmembrane subunit of MERS-S are required for efficient proteolysis. However, blockade of proprotein convertases did not impact MERS-S-dependent transduction of target cells expressing high amounts of the viral receptor, DPP4, and did not modulate MERS-CoV infectivity. These results show that MERS-S is a substrate for proprotein convertases and demonstrate that processing by these enzymes is dispensable for S protein activation. Efforts to inhibit MERS-CoV infection by ...Continue Reading

References

May 20, 1998·Proceedings of the National Academy of Sciences of the United States of America·V E VolchkovH D Klenk
Oct 19, 2001·Proceedings of the National Academy of Sciences of the United States of America·O LenzW Garten
Oct 3, 2002·Nature Reviews. Molecular Cell Biology·Gary Thomas
Dec 15, 2004·Biochemical and Biophysical Research Communications·Eric BergeronNabil G Seidah
Jan 24, 2006·Molecular and Cellular Biology·Tom S KimPeter S Nelson
May 27, 2011·Journal of Virology·Kazuya ShiratoFumihiro Taguchi
Nov 15, 2011·The Journal of Infectious Diseases·Annika KühlStefan Pöhlmann
Apr 28, 2012·The Journal of Biological Chemistry·Gero L BeckerTorsten Steinmetzer
May 17, 2012·Viruses·Taylor Heald-Sargent, Tom Gallagher
Jun 12, 2012·Nature Reviews. Drug Discovery·Nabil G Seidah, Annik Prat
Jun 28, 2012·International Journal of Oncology·Claire H Wilson, Catherine A Abbott
Jul 21, 2012·Viruses·Sandrine BelouzardGary R Whittaker
Oct 19, 2012·The New England Journal of Medicine·Ali M ZakiRon A M Fouchier
Apr 25, 2013·Antiviral Research·Antonella PasquatoStefan Kunz
Jun 21, 2013·The Lancet Infectious Diseases·Christian DrostenClemens-Martin Wendtner
Sep 10, 2013·Antiviral Research·Rolf Hilgenfeld, Malik Peiris
Nov 5, 2013·Antiviral Research·Jan Felix DrexlerChristian Drosten
Nov 13, 2013·Nature Reviews. Microbiology·Rachel L GrahamRalph S Baric

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Citations

Jan 23, 2016·Frontiers of Medicine·Mahmoud M ShehataGhazi Kayali
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jung-Eun ParkTom Gallagher
Sep 1, 2016·Annual Review of Virology·Fang Li
Dec 13, 2016·Expert Opinion on Therapeutic Targets·Lanying DuShibo Jiang
Mar 27, 2015·Clinical Microbiology Reviews·Jasper F W ChanKwok-Yung Yuen
Sep 28, 2018·Journal of Virology·Yuan ZhengFang Li
Mar 21, 2015·Expert Review of Respiratory Medicine·Jaffar A Al-Tawfiq, Ziad A Memish
Dec 13, 2019·Journal of Virology·Yushun WanFang Li
Nov 11, 2018·Scientific Reports·Hannah Kleine-WeberStefan Pöhlmann
May 12, 2020·Frontiers in Microbiology·Longping V TseRalph S Baric
Jul 25, 2020·Life Science Alliance·Dorothea BestleEva Böttcher-Friebertshäuser
Oct 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jean Kaoru Millet, Gary R Whittaker
Sep 12, 2020·Computational and Structural Biotechnology Journal·João Trigueiro-LouroHelena Rebelo-de-Andrade
Sep 22, 2020·Biochemical Pharmacology·Magda GioiaMassimo Coletta

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Methods Mentioned

BETA
transfection
electrophoresis
reverse-transcription PCR

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