HCV structural proteins interfere with interferon-alpha Jak/STAT signalling pathway

Hepatitis C virus (HCV) is remarkably efficient at establishing persistent infection. The current treatment with IFN-α given alone or in combination with ribavirin is ineffective in eliminating the virus in a large proportion of individuals with chronic hepatitis C. Recent data suggest that HCV bloc...

Full description

Saved in:
Bibliographic Details
Published in:Antiviral research 2007-11, Vol.76 (2), p.194-197
Main Authors: Luquin, Esther, Larrea, Esther, Civeira, Maria P., Prieto, Jesús, Aldabe, Rafael
Format: Article
Language:English
Subjects:
Antibiotics. Antiinfectious agents. Antiparasitic agents
Antiviral agents
Biological and medical sciences
Cell Line
Down-Regulation
Electrophoretic Mobility Shift Assay
HCV
Hepacivirus - immunology
Hepatitis C virus
Humans
Immunoblotting
Interferon
Interferon-alpha - immunology
Interferon-stimulated genes
Medical sciences
Pharmacology. Drug treatments
Replicon
Signal Transduction
STAT phosphorylation
STAT Transcription Factors - biosynthesis
Viral Nonstructural Proteins - immunology
Viral Structural Proteins - immunology
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Hepatitis C virus (HCV) is remarkably efficient at establishing persistent infection. The current treatment with IFN-α given alone or in combination with ribavirin is ineffective in eliminating the virus in a large proportion of individuals with chronic hepatitis C. Recent data suggest that HCV blocks IFN-α signalling, an effect that facilitates viral persistence. We have used the HCV genomic and subgenomic replicon system to analyze the effect of structural and non-structural viral proteins on the activation of the Jak/STAT pathway and induction of antiviral activity by IFN-α. Our results show that IFN-α-mediated STAT activation (but not IFN-γ-stimulated STAT phosphorylation) is blocked in Huh7 cell line containing the genomic replicon, while this is not observed in cells with the subgenomic replicon. In agreement with these findings, the transcriptional activity and the antiviral effect of IFN-α were significantly lower in cells harboring the genomic replicon than in cells with the subgenomic replicon. These results indicate that HCV structural proteins play an important role in the escape of HCV from the interferon system.
ISSN:0166-3542
1872-9096
DOI:10.1016/j.antiviral.2007.06.004