Next Article in Journal
Functional and Activity Analysis of Cattle UCP3 Promoter with MRFs-Related Factors
Next Article in Special Issue
The Effect of Minimally Invasive Hematoma Aspiration on the JNK Signal Transduction Pathway after Experimental Intracerebral Hemorrhage in Rats
Previous Article in Journal
Association of the MicroRNA-146a SNP rs2910164 with Ischemic Stroke Incidence and Prognosis in a Chinese Population
Article Menu
Issue 5 (May) cover image

Export Article

Open AccessArticle
Int. J. Mol. Sci. 2016, 17(5), 678; doi:10.3390/ijms17050678

SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6

1
Department of Medical Laboratory Science and Biotechnology, China Medical University, Taichung 404, Taiwan
2
Department of Biotechnology, College of Health Science, Asia University, Wufeng, Taichung 413, Taiwan
3
Department of Medical Genetics and Medical Research, China Medical University Hospital, Taichung 404, Taiwan
4
Department of Biotechnology and Laboratory Science in Medicine, National Yang Ming University, Taipei 112, Taiwan
*
Author to whom correspondence should be addressed.
Academic Editor: Atsushi Matsuzawa
Received: 14 March 2016 / Revised: 26 April 2016 / Accepted: 26 April 2016 / Published: 5 May 2016
(This article belongs to the Special Issue Kinase Signal Transduction)
View Full-Text   |   Download PDF [2015 KB, uploaded 5 May 2016]   |  

Abstract

Severe acute respiratory syndrome coronavirus (SARS-CoV) papain-like protease (PLPro) reportedly inhibits the production of type I interferons (IFNs) and pro-inflammatory cytokines in Toll-like receptor 3 (TLR3) and retinoic acid-inducible gene 1 (RIG-I) pathways. The study investigated the inhibitory effect and its antagonistic mechanism of SARS-CoV PLPro on TLR7-mediated cytokine production. TLR7 agonist (imiquimod (IMQ)) concentration-dependently induced activation of ISRE-, NF-κB- and AP-1-luciferase reporters, as well as the production of IFN-α, IFN-β, TNF-α, IL-6 and IL-8 in human promonocyte cells. However, SARS-CoV PLPro significantly inhibited IMQ-induced cytokine production through suppressing the activation of transcription factors IRF-3, NF-κB and AP-1. Western blot analysis with anti-Lys48 and anti-Lys63 ubiquitin antibodies indicated the SARS-CoV PLPro removed Lys63-linked ubiquitin chains of TRAF3 and TRAF6, but not Lys48-linked ubiquitin chains in un-treated and treated cells. The decrease in the activated state of TRAF3 and TRAF6 correlated with the inactivation of TBK1 in response to IMQ by PLPro. The results revealed that the antagonism of SARS-CoV PLPro on TLR7-mediated innate immunity was associated with the negative regulation of TRAF3/6-TBK1-IRF3/NF-κB/AP1 signals. View Full-Text
Keywords: SARS-CoV; Toll-like receptor 7; imiquimod; TRAF3; TRAF6; Lys63-linked polyubiquitin chains SARS-CoV; Toll-like receptor 7; imiquimod; TRAF3; TRAF6; Lys63-linked polyubiquitin chains
Figures

Figure 1

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Li, S.-W.; Wang, C.-Y.; Jou, Y.-J.; Huang, S.-H.; Hsiao, L.-H.; Wan, L.; Lin, Y.-J.; Kung, S.-H.; Lin, C.-W. SARS Coronavirus Papain-Like Protease Inhibits the TLR7 Signaling Pathway through Removing Lys63-Linked Polyubiquitination of TRAF3 and TRAF6. Int. J. Mol. Sci. 2016, 17, 678.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top