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Alcohol potentiates hepatitis C virus replicon expression

Authors

  • Ting Zhang,

    1. Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA
    2. Department of Infectious Diseases, The Children's Hospital of Fudan University, Shanghai, China
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  • Yuan Li,

    1. Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Jian-Ping Lai,

    1. Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Steven D. Douglas,

    1. Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • David S. Metzger,

    1. Department of Psychiatry, The Center for Studies of Addiction, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Charles P. O'Brien,

    1. Department of Psychiatry, The Center for Studies of Addiction, University of Pennsylvania School of Medicine, Philadelphia, PA
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  • Dr. Wen-Zhe Ho

    Corresponding author
    1. Division of Allergy and Immunology, Joseph Stokes Jr. Research Institute at The Children's Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA
    • Division of Allergy and Immunology, The Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th St. and Civic Center Blvd., Philadelphia, PA 19104. fax: 215-590-2025
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Abstract

Alcohol consumption accelerates liver damage and diminishes the anti-hepatitis C virus (HCV) effect of interferon alfa (IFN-α) in patients with HCV infection. It is unknown, however, whether alcohol enhances HCV replication and promotes HCV disease progression. The availability of the HCV replicon containing hepatic cells has provided a unique opportunity to investigate the interaction between alcohol and HCV replicon expression. We determined whether alcohol enhances HCV RNA expression in the replicon containing hepatic cells. Alcohol, in a concentration-dependent fashion, significantly increased HCV replicon expression. Alcohol also compromised the anti-HCV effect of IFN-α. Investigation of the mechanism(s) responsible for the alcohol action on HCV replicon indicated that alcohol activated nuclear factor κB (NF-κB) promoter. Caffeic acid phenethyl ester (CAPE), a specific inhibitor of the activation of NF-κB, abolished alcohol-induced HCV RNA expression. In addition, naltrexone, an opiate receptor antagonist, abrogated the enhancing effect of alcohol on HCV replicon expression. In conclusion, alcohol, probably through the activation of NF-κB and the endogenous opioid system, enhances HCV replicon expression and compromises the anti-HCV effect of IFN-α. Thus, alcohol may play an important role in vivo as a cofactor in HCV disease progression and compromise IFN-α-based therapy against HCV infection.

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