Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV

The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG) expression by...

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Published in:PloS one 2011-11, Vol.6 (11), p.e27866
Main Authors: Stevenson, Nigel J, Murphy, Alison G, Bourke, Nollaig M, Keogh, Catherine A, Hegarty, John E, O'Farrelly, Cliona
Format: Article
Language:English
Subjects:
Antiviral agents
Antiviral Agents - pharmacology
Antiviral drugs
Biology
Blotting, Western
Cells, Cultured
Core protein
Fluorescent Antibody Technique
Gene expression
GTP-Binding Proteins - genetics
GTP-Binding Proteins - metabolism
Hepacivirus - drug effects
Hepacivirus - immunology
Hepacivirus - metabolism
Hepatitis C - drug therapy
Hepatitis C - immunology
Hepatitis C - virology
Hepatocytes
Hepatocytes - drug effects
Hepatocytes - immunology
Hepatocytes - metabolism
Humans
Immunity
Immunoenzyme Techniques
Immunomodulation
Immunoprecipitation
Interferon
Interferon-alpha - pharmacology
Kinases
Medicine
mRNA
Myxovirus Resistance Proteins
Nucleoside analogs
Phosphorylation
Phosphorylation - drug effects
Real-Time Polymerase Chain Reaction
Ribavirin
Ribavirin - pharmacology
RNA, Messenger - genetics
Rodents
Signal transduction
Signal Transduction - drug effects
Signal Transduction - genetics
Signaling
Stat1 protein
STAT1 Transcription Factor - genetics
STAT1 Transcription Factor - metabolism
Stat3 protein
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
Viral Core Proteins - genetics
Viral Core Proteins - metabolism
Viral infections
Virus Replication - drug effects
Virus Replication - immunology
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description The nucleoside analogue Ribavirin significantly increases patient response to IFN-α treatment of HCV, by directly inhibiting viral replication. Recent studies indicate that Ribavirin also regulates immunity and we propose that Ribavirin enhances specific interferon sensitive gene (ISG) expression by amplifying the IFN-α-JAK/STAT pathway. We found that IFN-α-induced STAT1 and STAT3 phosphorylation was increased in hepatocytes co-treated with Ribavirin and IFN-α, compared to IFN-α alone. Ribavirin specifically enhanced IFN-α induced mRNA and protein of the anti-viral mediator MxA, which co-localised with HCV core protein. These novel findings indicate for the first time that Ribavirin, in addition to its viral incorporation, also enhances IFN-α-JAK/STAT signalling, leading to a novel MxA-mediated immuno-modulatory mechanism that may enhance IFN-α anti-viral activity against HCV.
doi_str_mv 10.1371/journal.pone.0027866
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subjects Antiviral agents
Antiviral Agents - pharmacology
Antiviral drugs
Biology
Blotting, Western
Cells, Cultured
Core protein
Fluorescent Antibody Technique
Gene expression
GTP-Binding Proteins - genetics
GTP-Binding Proteins - metabolism
Hepacivirus - drug effects
Hepacivirus - immunology
Hepacivirus - metabolism
Hepatitis C - drug therapy
Hepatitis C - immunology
Hepatitis C - virology
Hepatocytes
Hepatocytes - drug effects
Hepatocytes - immunology
Hepatocytes - metabolism
Humans
Immunity
Immunoenzyme Techniques
Immunomodulation
Immunoprecipitation
Interferon
Interferon-alpha - pharmacology
Kinases
Medicine
mRNA
Myxovirus Resistance Proteins
Nucleoside analogs
Phosphorylation
Phosphorylation - drug effects
Real-Time Polymerase Chain Reaction
Ribavirin
Ribavirin - pharmacology
RNA, Messenger - genetics
Rodents
Signal transduction
Signal Transduction - drug effects
Signal Transduction - genetics
Signaling
Stat1 protein
STAT1 Transcription Factor - genetics
STAT1 Transcription Factor - metabolism
Stat3 protein
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
Viral Core Proteins - genetics
Viral Core Proteins - metabolism
Viral infections
Virus Replication - drug effects
Virus Replication - immunology
title Ribavirin enhances IFN-α signalling and MxA expression: a novel immune modulation mechanism during treatment of HCV
url http://sfxeu10.hosted.exlibrisgroup.com/loughborough?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-17T04%3A35%3A31IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Ribavirin%20enhances%20IFN-%CE%B1%20signalling%20and%20MxA%20expression:%20a%20novel%20immune%20modulation%20mechanism%20during%20treatment%20of%20HCV&rft.jtitle=PloS%20one&rft.au=Stevenson,%20Nigel%20J&rft.date=2011-11-16&rft.volume=6&rft.issue=11&rft.spage=e27866&rft.pages=e27866-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0027866&rft_dat=%3Cproquest_plos_%3E2900467091%3C/proquest_plos_%3E%3Cgrp_id%3Ecdi_FETCH-LOGICAL-c525t-148f578a00cbb9235265ff663a77aaf3d44ecd8da2c5ffd4c025ad202517024d3%3C/grp_id%3E%3Coa%3E%3C/oa%3E%3Curl%3E%3C/url%3E&rft_id=info:oai/&rft_pqid=1312159208&rft_id=info:pmid/22114715&rfr_iscdi=true