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Inhibition of proprotein convertases abrogates processing of the middle eastern respiratory syndrome coronavirus spike protein in infected cells but does not reduce viral infectivity.
- Source :
-
The Journal of infectious diseases [J Infect Dis] 2015 Mar 15; Vol. 211 (6), pp. 889-97. Date of Electronic Publication: 2014 Jul 23. - Publication Year :
- 2015
-
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 targeting host cell proteases should therefore focus on enzymes that process MERS-S during viral uptake into target cells.<br /> (© The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Subjects :
- Amino Acid Sequence
Antiviral Agents pharmacology
Drug Evaluation, Preclinical
HEK293 Cells
Humans
Molecular Sequence Data
Protease Inhibitors pharmacology
Protein Processing, Post-Translational
Proteolysis
Spike Glycoprotein, Coronavirus chemistry
Virus Internalization
Coronavirus physiology
Proprotein Convertases antagonists & inhibitors
Spike Glycoprotein, Coronavirus metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1537-6613
- Volume :
- 211
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- The Journal of infectious diseases
- Publication Type :
- Academic Journal
- Accession number :
- 25057042
- Full Text :
- https://doi.org/10.1093/infdis/jiu407