The green tea polyphenol, epigallocatechin-3-gallate, inhibits hepatitis C virus entry

Authors

  • Sandra Ciesek,

    Corresponding author
    1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
    2. Division of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), Hannover, Germany
    • Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Carl-Neuberg Straße 1, 30625 Hannover, Germany
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    • fax: +49 511 220027186

  • Thomas von Hahn,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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  • Che C. Colpitts,

    1. Departments of Biochemistry and Medical Microbiology and Immunology and Li Ka Shing Insitute of Virology, University of Alberta, Edmonton, Alberta, Canada
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  • Luis M. Schang,

    1. Departments of Biochemistry and Medical Microbiology and Immunology and Li Ka Shing Insitute of Virology, University of Alberta, Edmonton, Alberta, Canada
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  • Martina Friesland,

    1. Division of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), Hannover, Germany
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  • Jörg Steinmann,

    1. Institute of Medical Microbiology, University Hospital Essen, Essen, Germany
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  • Michael P. Manns,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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  • Michael Ott,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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  • Heiner Wedemeyer,

    1. Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany
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  • Philip Meuleman,

    1. Center for Vaccinology, Ghent University and Hospital, Ghent, Belgium
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  • Thomas Pietschmann,

    1. Division of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), Hannover, Germany
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  • Eike Steinmann

    1. Division of Experimental Virology, TWINCORE, Center for Experimental and Clinical Infection Research; a joint venture between the Medical School Hannover (MHH) and the Helmholtz Center for Infection Research (HZI), Hannover, Germany
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  • Potential conflict of interest: Dr. Schang is a consultant for Epiphany Biosciences.

  • This work was supported by grants from the Deutsche Forschungsgemeinschaft (DFG) (HA 4393/2-1; to T.V.H.) and (Ci 171/2-1; to S.C.) and from the CIHR and BWF (to L.M.S.). T.P. was supported by grants from the Helmholtz Association SO-024 and the DFG (PI 734/2-1 and SFB 900, Teilprojekt A6). E.S. was supported by an intramural young investigator award of the Helmholtz Center for Infection Research and the DFG (STE 1954/1-1). C.C.C. was supported by the NSERC and AHFMR.

Abstract

Hepatitis C virus (HCV) is a major cause of liver cirrhosis and hepatocellular carcinoma. Current antiviral therapy fails to clear infection in a substantial proportion of cases. Drug development is focused on nonstructural proteins required for RNA replication. Individuals undergoing orthotopic liver transplantation face rapid, universal reinfection of the graft. Therefore, antiviral strategies targeting the early stages of infection are urgently needed for the prevention of HCV infection. In this study, we identified the polyphenol, epigallocatechin-3-gallate (EGCG), as an inhibitor of HCV entry. Green tea catechins, such as EGCG and its derivatives, epigallocatechin (EGC), epicatechin gallate (ECG), and epicatechin (EC), have been previously found to exert antiviral and antioncogenic properties. EGCG had no effect on HCV RNA replication, assembly, or release of progeny virions. However, it potently inhibited Cell-culture–derived HCV (HCVcc) entry into hepatoma cell lines as well as primary human hepatocytes. The effect was independent of the HCV genotype, and both infection of cells by extracellular virions and cell-to-cell spread were blocked. Pretreatment of cells with EGCG before HCV inoculation did not reduce HCV infection, whereas the application of EGCG during inoculation strongly inhibited HCV infectivity. Moreover, treatment with EGCG directly during inoculation strongly inhibited HCV infectivity. Expression levels of all known HCV (co-)receptors were unaltered by EGCG. Finally, we showed that EGCG inhibits viral attachment to the cell, thus disrupting the initial step of HCV cell entry. Conclusion: The green tea molecule, EGCG, potently inhibits HCV entry and could be part of an antiviral strategy aimed at the prevention of HCV reinfection after liver transplantation. (HEPATOLOGY 2011)

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