Evidence that TMPRSS2 activates the severe acute respiratory syndrome coronavirus spike protein for membrane fusion and reduces viral control by the humoral immune response

Journal of Virology
Ilona GlowackaStefan Pöhlmann

Abstract

The spike (S) protein of the severe acute respiratory syndrome coronavirus (SARS-CoV) can be proteolytically activated by cathepsins B and L upon viral uptake into target cell endosomes. In contrast, it is largely unknown whether host cell proteases located in the secretory pathway of infected cells and/or on the surface of target cells can cleave SARS S. We along with others could previously show that the type II transmembrane protease TMPRSS2 activates the influenza virus hemagglutinin and the human metapneumovirus F protein by cleavage. Here, we assessed whether SARS S is proteolytically processed by TMPRSS2. Western blot analysis revealed that SARS S was cleaved into several fragments upon coexpression of TMPRSS2 (cis-cleavage) and upon contact between SARS S-expressing cells and TMPRSS2-positive cells (trans-cleavage). cis-cleavage resulted in release of SARS S fragments into the cellular supernatant and in inhibition of antibody-mediated neutralization, most likely because SARS S fragments function as antibody decoys. trans-cleavage activated SARS S on effector cells for fusion with target cells and allowed efficient SARS S-driven viral entry into targets treated with a lysosomotropic agent or a cathepsin inhibitor. Final...Continue Reading

References

Apr 21, 1999·Trends in Microbiology·W Garten, H D Klenk
Sep 30, 2000·Bioorganic & Medicinal Chemistry Letters·W LubischA Möller
Jun 8, 2001·Annual Review of Biochemistry·D M Eckert, P S Kim
Jun 5, 2003·Lancet·John M NichollsJ S Malik Peiris
Dec 4, 2003·Biochemical and Biophysical Research Communications·Xiaodong XiaoDimiter S Dimitrov
Dec 13, 2003·The Journal of Biological Chemistry·Swee Kee WongMichael Farzan
Jan 7, 2004·Biochemical and Biophysical Research Communications·Aleksandar RadonićAndreas Nitsche
Feb 10, 2004·Biochemical and Biophysical Research Communications·Peigang WangHongkui Deng
Mar 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Mar 20, 2004·The Journal of Infectious Diseases·Xinchun ChenXiaohua Le
Apr 23, 2004·The EMBO Journal·Olga DolnikViktor Volchkov
Jun 15, 2004·The Journal of Infectious Diseases·Yong Xiu YaoIan M Jones
Sep 10, 2004·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuxian HeShibo Jiang
Sep 11, 2004·Biochemical and Biophysical Research Communications·Yuchun NieHongkui Deng
Sep 24, 2004·Trends in Microbiology·Heike Hofmann, Stefan Pöhlmann
Dec 4, 2004·Nature Medicine·J S M PeirisK Y Yuen
Dec 15, 2004·Biochemical and Biophysical Research Communications·Eric BergeronNabil G Seidah
Mar 26, 2005·The EMBO Journal·Wenhui LiMichael Farzan
Apr 9, 2005·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yuxian HeShibo Jiang
Aug 6, 2005·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Aug 24, 2005·Proceedings of the National Academy of Sciences of the United States of America·Shutoku MatsuyamaFumihiro Taguchi
Sep 20, 2005·Proceedings of the National Academy of Sciences of the United States of America·Susanna K P LauKwok-Yung Yuen
Oct 1, 2005·Science·Wendong LiLin-Fa Wang
Jan 24, 2006·Molecular and Cellular Biology·Tom S KimPeter S Nelson

❮ Previous
Next ❯

Citations

Nov 15, 2011·The Journal of Infectious Diseases·Annika KühlStefan Pöhlmann
May 27, 2011·Journal of Virology·Kazuya ShiratoFumihiro Taguchi
Nov 11, 2011·Journal of Virology·Rachel M NygaardLeslie A Schiff
Dec 14, 2012·PLoS Neglected Tropical Diseases·Andrea MarziHeinz Feldmann
Dec 19, 2013·PLoS Pathogens·Bastian HatesuerKlaus Schughart
Jul 19, 2011·Future Virology·Dale L Barnard, Yohichi Kumaki
Jul 21, 2012·Viruses·Sandrine BelouzardGary R Whittaker
Feb 8, 2016·Virology Journal·Hulda R Jonsdottir, Ronald Dijkman
Dec 20, 2011·Current Opinion in Virology·Meagan BollesRalph Baric
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
Dec 3, 2014·Virus Research·Jean Kaoru Millet, Gary R Whittaker
Apr 29, 2015·Oncogene·P Adamo, M R Ladomery
Apr 25, 2015·Biochemistry·Haizhi WangAleister Saunders
Feb 11, 2015·Antiviral Research·Yanchen ZhouGraham Simmons
Dec 3, 2014·Virus Research·Juan RegueraJosé M Casasnovas
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
Sep 1, 2016·Annual Review of Virology·Fang Li
May 17, 2012·Viruses·Taylor Heald-Sargent, Tom Gallagher

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.