Scavenger receptor class B type I is a key host factor for hepatitis C virus infection required for an entry step closely linked to CD81

Authors

  • Mirjam B. Zeisel,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
    3. Department of Medicine II, University of Freiburg, Germany
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  • George Koutsoudakis,

    1. Department for Molecular Virology, University of Heidelberg, Germany
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  • Eva K. Schnober,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
    3. Department of Medicine II, University of Freiburg, Germany
    4. Faculty of Biology, University of Freiburg, Germany
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  • Anita Haberstroh,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
    3. Department of Medicine II, University of Freiburg, Germany
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  • Hubert E. Blum,

    1. Department of Medicine II, University of Freiburg, Germany
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  • François-Loïc Cosset,

    1. INSERM, U758, Lyon, France
    2. Ecole Normale Supérieure de Lyon, Lyon, France
    3. IFR128 BioSciences Lyon-Gerland, Lyon, France
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  • Takaji Wakita,

    1. Department of Microbiology, Tokyo Metropolitan Institute for Neuroscience, Tokyo, Japan
    Current affiliation:
    1. National Institute of Infectious Diseases, Department of Virology II, Tokyo, Japan
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  • Daniel Jaeck,

    1. Centre de Chirurgie Viscérale, Hépatique et de Transplantation Multiorganes, Université Louis Pasteur, Strasbourg, France
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  • Michel Doffoel,

    1. Service d'Hépatogastroentérologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
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  • Cathy Royer,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
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  • Eric Soulier,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
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  • Evelyne Schvoerer,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
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  • Catherine Schuster,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
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  • Françoise Stoll-Keller,

    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
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  • Ralf Bartenschlager,

    1. Department for Molecular Virology, University of Heidelberg, Germany
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  • Thomas Pietschmann,

    1. Department for Molecular Virology, University of Heidelberg, Germany
    Current affiliation:
    1. TWINCORE—Center for Experimental and Clinical Infection Research, Department Experimental Virology, Hannover, Germany
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  • Heidi Barth,

    1. Department of Medicine II, University of Freiburg, Germany
    Current affiliation:
    1. Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD
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  • Thomas F. Baumert

    Corresponding author
    1. Institut National de la Santé et de la Recherche Médicale (INSERM), U748, Strasbourg, France
    2. Université Louis Pasteur, Strasbourg, France
    3. Department of Medicine II, University of Freiburg, Germany
    4. Service d'Hépatogastroentérologie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France
    • INSERM Unité 748, Université Louis Pasteur, 3 Rue Koeberlé, F-67000 Strasbourg, France
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    • fax: (33) 3-90-24-37-24


  • Potential conflict of interest: Nothing to report.

Abstract

Hepatitis C virus (HCV) is a major cause of chronic hepatitis worldwide. Scavenger receptor class B type I (SR-BI) has been shown to bind HCV envelope glycoprotein E2, participate in entry of HCV pseudotype particles, and modulate HCV infection. However, the functional role of SR-BI for productive HCV infection remains unclear. In this study, we investigated the role of SR-BI as an entry factor for infection of human hepatoma cells using cell culture–derived HCV (HCVcc). Anti–SR-BI antibodies directed against epitopes of the human SR-BI extracellular loop specifically inhibited HCVcc infection in a dose-dependent manner. Down-regulation of SR-BI expression by SR-BI–specific short interfering RNAs (siRNAs) markedly reduced the susceptibility of human hepatoma cells to HCVcc infection. Kinetic studies demonstrated that SR-BI acts predominately after binding of HCV at an entry step occurring at a similar time point as CD81–HCV interaction. Although the addition of high-density lipoprotein (HDL) enhanced the efficiency of HCVcc infection, anti–SR-BI antibodies and SR-BI–specific siRNA efficiently inhibited HCV infection independent of lipoprotein. Conclusion: Our data suggest that SR-BI (i) represents a key host factor for HCV entry, (ii) is implicated in the same HCV entry pathway as CD81, and (iii) targets an entry step closely linked to HCV–CD81 interaction. (HEPATOLOGY 2007.)

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