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Original Paper

Free Access

Bile Acids Promote HCV Replication through the EGFR/ERK Pathway in Replicon-Harboring Cells

Patton J.B. · George D. · Chang K.-O.

Author affiliations

Department of Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, Manhattan, Kans., USA

Corresponding Author

Dr. Kyeong-Ok Chang

Department of Diagnostic Medicine and Pathobiology

College of Veterinary Medicine, Kansas State University

1800 Denison Avenue, Manhattan, KS 66506 (USA)

Tel. +1 785 532 3849, Fax +1 785 532 4039, E-Mail kchang@vet.ksu.edu

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Intervirology 2011;54:339–348

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Abstract

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.

© 2011 S. Karger AG, Basel


Article / Publication Details

First-Page Preview
Abstract of Original Paper

Received: February 08, 2010
Accepted: September 20, 2010
Published online: February 05, 2011
Issue release date: October 2011

Number of Print Pages: 10
Number of Figures: 5
Number of Tables: 1

ISSN: 0300-5526 (Print)
eISSN: 1423-0100 (Online)

For additional information: http://www.karger.com/INT


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