| Bile acids promote HCV replication through the EGFR/ERK pathway in replicon-harboring cells. | |
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MedLine Citation:
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PMID: 21293096 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVES: Bile acids promoted the replication of hepatitis C virus (HCV) and compromised the anti-HCV effects of interferon-α (IFN-α) in replicon-harboring cells. To explore a potential mechanism for the observation, we studied the effects of bile acids on the epidermal growth factor receptor (EGFR) and the extracellular signal-regulated kinase (ERK) pathway in association with HCV replication in genotype 1a or 1b replicon-harboring cells. METHODS: Replicon-harboring cells were treated with various bile acids, IFN-α and small molecule inhibitors either individually or combined together. The effects of these treatments were measured using cell cycle analysis, qRT-PCR, and Western blot analysis. RESULTS: Bile acids induced the activation of EGFR/ERK pathway and extended S-phase of cells, which was correlated with the increased levels of viral replication. The inhibitors of EGFR (AG1478) or ERK (U0126) significantly mitigated the bile acid-mediated promotion of HCV replication. When AG1478 or U0126 were added to the treatment of bile acids and IFN-α, they were able to restore the anti-HCV effects of IFN-α. CONCLUSION: Our data suggest that the addition of an EGFR or ERK inhibitor to the current IFN-α-based regimen may improve overall treatment efficacy by blocking the bile acid-mediated promotion of HCV replication. |
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Authors:
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John B Patton; David George; Kyeong-Ok Chang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural Date: 2011-02-05 |
Journal Detail:
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Title: Intervirology Volume: 54 ISSN: 1423-0100 ISO Abbreviation: Intervirology Publication Date: 2011 |
Date Detail:
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Created Date: 2011-10-11 Completed Date: 2012-02-29 Revised Date: 2013-02-08 |
Medline Journal Info:
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Nlm Unique ID: 0364265 Medline TA: Intervirology Country: Switzerland |
Other Details:
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Languages: eng Pagination: 339-48 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 S. Karger AG, Basel. |
Affiliation:
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Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kans. 66506, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antiviral Agents
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pharmacology Bile Acids and Salts / pharmacology*, physiology Cell Cycle Cell Line Chenodeoxycholic Acid / pharmacology Extracellular Signal-Regulated MAP Kinases / antagonists & inhibitors, metabolism* Genes, Reporter Hepacivirus / physiology* Hepatitis C / drug therapy Humans Interferon-alpha / pharmacology Interphase Luciferases, Renilla / biosynthesis, genetics Promoter Regions, Genetic Quinazolines / pharmacology Receptor, Epidermal Growth Factor / antagonists & inhibitors, metabolism* Transcriptional Activation Tyrphostins / pharmacology Viral Nonstructural Proteins / metabolism Virus Replication* |
| Grant Support | |
ID/Acronym/Agency:
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P20RR016443/RR/NCRR NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antiviral Agents; 0/Bile Acids and Salts; 0/Interferon-alpha; 0/NS-5 protein, hepatitis C virus; 0/Quinazolines; 0/Tyrphostins; 0/Viral Nonstructural Proteins; 170449-18-0/tyrphostin AG 1478; 474-25-9/Chenodeoxycholic Acid; EC 1.13.12.5/Luciferases, Renilla; EC 2.7.10.1/Receptor, Epidermal Growth Factor; EC 2.7.11.24/Extracellular Signal-Regulated MAP Kinases |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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