Middle East Respiratory Syndrome Coronavirus Spike Protein Is Not Activated Directly by Cellular Furin during Viral Entry into Target Cells

Journal of Virology
Shutoku MatsuyamaWataru Kamitani

Abstract

Middle East respiratory syndrome coronavirus (MERS-CoV) utilizes host cellular proteases to enter cells. A previous report shows that furin, which is distributed mainly in the Golgi apparatus and cycled to the cell surface and endosomes, proteolytically activates the MERS-CoV spike (S) protein following receptor binding to mediate fusion between the viral and cellular membranes. In this study, we reexamined furin usage by MERS-CoV using a real-time PCR-based virus cell entry assay after inhibition of cellular proteases. We found that the furin inhibitor dec-RVKR-CMK blocked entry of MERS-CoV harboring an S protein lacking furin cleavage sites; it even blocked entry into furin-deficient LoVo cells. In addition, dec-RVKR-CMK inhibited not only the enzymatic activity of furin but also those of cathepsin L, cathepsin B, trypsin, papain, and TMPRSS2. Furthermore, a virus cell entry assay and a cell-cell fusion assay provided no evidence that the S protein was activated by exogenous furin. Therefore, we conclude that furin does not play a role in entry of MERS-CoV into cells and that the inhibitory effect of dec-RVKR-CMK is specific for TMPRSS2 and cathepsin L rather than furin.IMPORTANCE Previous studies using the furin inhibitor de...Continue Reading

References

Sep 15, 1993·Biochemical and Biophysical Research Communications·S TakahashiK Nakayama
Oct 3, 2002·Nature Reviews. Molecular Cell Biology·Gary Thomas
Mar 11, 2004·Proceedings of the National Academy of Sciences of the United States of America·Graham SimmonsPaul Bates
Oct 11, 2005·Journal of Molecular Medicine : Official Organ of the Gesellschaft Deutscher Naturforscher Und Ärzte·Ajoy Basak
Apr 9, 2008·Neoplasia : an International Journal for Oncology Research·Julia M CoppolaAlnawaz Rehemtulla
Mar 27, 2009·Proceedings of the National Academy of Sciences of the United States of America·Sandrine BelouzardGary R Whittaker
Apr 1, 2009·The Journal of Biological Chemistry·Tomoko KomiyamaRobert S Fuller
Apr 28, 2012·The Journal of Biological Chemistry·Gero L BeckerTorsten Steinmetzer
May 17, 2012·Viruses·Taylor Heald-Sargent, Tom Gallagher
Apr 27, 2013·The Journal of General Virology·Adriaan H de WildeBernadette G van den Hoogen
Oct 8, 2014·Proceedings of the National Academy of Sciences of the United States of America·Jean Kaoru Millet, Gary R Whittaker
Dec 3, 2014·Virus Research·Jean Kaoru Millet, Gary R Whittaker
Mar 5, 2016·Traffic·Judith M White, Gary R Whittaker
Oct 30, 2016·Proceedings of the National Academy of Sciences of the United States of America·Jung-Eun ParkTom Gallagher
May 1, 2017·Biochemical Pharmacology·Andres J Klein-Szanto, Daniel E Bassi

❮ Previous
Next ❯

Citations

Sep 28, 2018·Journal of Virology·Yuan ZhengFang Li
May 6, 2019·Cell Communication and Signaling : CCS·Katarzyna OwczarekKrzysztof Pyrc
May 28, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Elisa BarileMaurizio Pellecchia
Jun 25, 2020·Microbiology and Immunology·Fumihiro KatoMakoto Takeda
Aug 11, 2020·Médecine sciences : M/S·Erwan SallardÉtienne Decroly
Nov 11, 2018·Scientific Reports·Hannah Kleine-WeberStefan Pöhlmann
Mar 14, 2020·Proceedings of the National Academy of Sciences of the United States of America·Shutoku MatsuyamaMakoto Takeda
Jul 25, 2020·Life Science Alliance·Dorothea BestleEva Böttcher-Friebertshäuser
Nov 26, 2020·Science Signaling·Aleksandra MilewskaKrzysztof Pyrc
Oct 13, 2020·IScience·Canrong WuHua Li
Feb 10, 2021·Environmental Chemistry Letters·Erwan SallardJacques van Helden
Mar 30, 2021·European Journal of Pharmaceutical Sciences : Official Journal of the European Federation for Pharmaceutical Sciences·Sagar BargeJagat Borah
Oct 29, 2020·ACS Infectious Diseases·Anil Mathew TharappelHongmin Li
Apr 2, 2021·Journal of Virology·Yuriko TomitaMakoto Takeda
Aug 3, 2021·Molecular Systems Biology·Fangyuan ChenIvet Bahar
Aug 3, 2021·Reviews in Medical Virology·Mina Mobini KeshehMilad Zandi
Oct 15, 2021·Journal of Biomolecular Structure & Dynamics·Essam S A E H KhattabAhmed A Elhenawy

❮ 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.