Methamphetamine enhances Hepatitis C virus replication in human hepatocytes

Authors

  • L. Ye,

    1. Division of Allergy & Immunology, Joseph Stokes, Jr. Research Institute at The Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
    2. State Key Laboratory of Virology, College of Life Sciences, Wuhan University, Hubei, China
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  • J. S. Peng,

    1. Wuhan Centers for Disease Control and Prevention, Wuhan, Hubei, China
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  • X. Wang,

    1. Division of Allergy & Immunology, Joseph Stokes, Jr. Research Institute at The Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • Y. J. Wang,

    1. Division of Allergy & Immunology, Joseph Stokes, Jr. Research Institute at The Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • G. X. Luo,

    1. Division of Allergy & Immunology, Joseph Stokes, Jr. Research Institute at The Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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  • W. Z. Ho

    1. Division of Allergy & Immunology, Joseph Stokes, Jr. Research Institute at The Children’s Hospital of Philadelphia, Department of Pediatrics, University of Pennsylvania School of Medicine, Philadelphia, PA, USA
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Wen-Zhe Ho, Division of Allergy & Immunology, The Children’s Hospital of Philadelphia, University of Pennsylvania School of Medicine, 34th Street & Civic Center Boulevard, Philadelphia, PA 19104, USA. Tel.: +1 215 590 4462; Fax: +1 215 590 2025; E-mail: ho@email.chop.edu

Abstract

Summary.  Very little is known about the interactions between hepatitis C virus (HCV) and methamphetamine, which is a highly abused psychostimulant and a known risk factor for human immunodeficiency virus (HIV)/HCV infection. This study examined whether methamphetamine has the ability to inhibit innate immunity in the host cells, facilitating HCV replication in human hepatocytes. Methamphetamine inhibited intracellular interferon alpha expression in human hepatocytes, which was associated with the increase in HCV replication. In addition, methamphetamine also compromised the anti-HCV effect of recombinant interferon alpha. Further investigation of mechanism(s) responsible for the methamphetamine action revealed that methamphetamine was able to inhibit the expression of the signal transducer and activator of transcription 1, a key modulator in interferon-mediated immune and biological responses. Methamphetamine also down-regulated the expression of interferon regulatory factor-5, a crucial transcriptional factor that activates the interferon pathway. These in vitro findings that methamphetamine compromises interferon alpha-mediated innate immunity against HCV infection indicate that methamphetamine may have a cofactor role in the immunopathogenesis of HCV disease.

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