Get 20M+ Full-Text Papers For Less Than $1.50/day. Start a 14-Day Trial for You or Your Team.

Learn More →

Double-stranded RNA-induced interferon-beta and inflammatory cytokine production modulated by hepatitis C virus serine proteases derived from patients with hepatic diseases

Double-stranded RNA-induced interferon-beta and inflammatory cytokine production modulated by... We previously demonstrated that hepatitis C virus (HCV) serine protease NS3-4A was unable to cleave TRIF (adaptor protein of Toll-like receptor 3), resulting in a lack of suppression of the TRIF-mediated pathway, whereas NS3-4A cleaved Cardif (adaptor protein of retinoic acid-inducible gene I or melanoma differentiation-associated gene-5), resulting in an interruption of the Cardif-mediated pathway in non-neoplastic human hepatocyte PH5CH8 cells. To elucidate these observations, we examined the cleavage potential of NS3-4A for TRIF in PH5CH8 cells, genome-length HCV RNA-replicating O cells, and HCV-infected cells, and we demonstrated that NS3-4A lacked the ability to cleave endogenous TRIF, regardless of HCV strains derived from patients with different stages of hepatic disease. Furthermore, we demonstrated that inflammatory cytokine production by NF-κB activation via the TRIF-mediated pathway also remained unsuppressed by NS3-4A. These results suggest that the inhibitory effects of NS3-4A on antiviral signaling pathways are limited to the Cardif-mediated pathway in human hepatocytes. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

Double-stranded RNA-induced interferon-beta and inflammatory cytokine production modulated by hepatitis C virus serine proteases derived from patients with hepatic diseases

Download PDF
10 pages

Loading next page...
 
/lp/springer_journal/double-stranded-rna-induced-interferon-beta-and-inflammatory-cytokine-yIyEBEe5q0

References (42)

Publisher
Springer Journals
Copyright
Copyright © 2009 by Springer-Verlag
Subject
Biomedicine; Infectious Diseases; Medical Microbiology ; Virology
ISSN
0304-8608
eISSN
1432-8798
DOI
10.1007/s00705-009-0375-z
pmid
19353241
Publisher site
See Article on Publisher Site

Abstract

We previously demonstrated that hepatitis C virus (HCV) serine protease NS3-4A was unable to cleave TRIF (adaptor protein of Toll-like receptor 3), resulting in a lack of suppression of the TRIF-mediated pathway, whereas NS3-4A cleaved Cardif (adaptor protein of retinoic acid-inducible gene I or melanoma differentiation-associated gene-5), resulting in an interruption of the Cardif-mediated pathway in non-neoplastic human hepatocyte PH5CH8 cells. To elucidate these observations, we examined the cleavage potential of NS3-4A for TRIF in PH5CH8 cells, genome-length HCV RNA-replicating O cells, and HCV-infected cells, and we demonstrated that NS3-4A lacked the ability to cleave endogenous TRIF, regardless of HCV strains derived from patients with different stages of hepatic disease. Furthermore, we demonstrated that inflammatory cytokine production by NF-κB activation via the TRIF-mediated pathway also remained unsuppressed by NS3-4A. These results suggest that the inhibitory effects of NS3-4A on antiviral signaling pathways are limited to the Cardif-mediated pathway in human hepatocytes.

Journal

Archives of Virology – Springer Journals

Published: May 1, 2009

There are no references for this article.