Hepatitis C virus core protein binds to apolipoprotein AII and its secretion is modulated by fibrates

Authors

  • Abdelmajid Sabile,

    1. Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unité 370, Faculté de Médecine Necker-Enfants Malades, Paris, France
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  • Gabriel Perlemuter,

    1. Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unité 370, Faculté de Médecine Necker-Enfants Malades, Paris, France
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  • Fulvia Bono,

    1. Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unité 370, Faculté de Médecine Necker-Enfants Malades, Paris, France
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  • Kyoko Kohara,

    1. Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
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  • France Demaugre,

    1. Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unité 370, Faculté de Médecine Necker-Enfants Malades, Paris, France
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  • Michinori Kohara,

    1. Department of Microbiology and Cell Biology, The Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan
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  • Yoshiharu Matsuura,

    1. Department of Virology II, National Institute of Health, Tokyo, Japan
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  • Tatsuo Miyamura,

    1. Department of Virology II, National Institute of Health, Tokyo, Japan
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  • Christian Bréchot M.D., Ph.D.,

    Corresponding author
    1. Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unité 370, Faculté de Médecine Necker-Enfants Malades, Paris, France
    • Carcinogenèse hépatique et Virologie Moléculaire, INSERM U 370, Faculté de Médecine Necker-Enfants Malades, 156 rue de Vaugirard, 75730 Paris Cedex 15, France. fax: (33) 1 40 61 55 81
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  • Giovanna Barba

    1. Liver Cancer and Molecular Virology, Institut National de la Santé et de la Recherche Médicale Unité 370, Faculté de Médecine Necker-Enfants Malades, Paris, France
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Abstract

Several lines of evidence suggest that hepatitis C virus (HCV) core protein may modulate cellular transduction signals and alter lipid metabolism. We have investigated the binding of HCV core protein to cellular proteins by combining 2 yeast hybrid, confocal, and surface plasmon resonance assays. Our results show the direct binding of the viral protein to apolipoprotein AII (apoAII) and map the interaction domain to the C-terminal of HCV core protein. To investigate the biological relevance of the interaction between HCV core and lipid metabolism, we took advantage of the well-established increase in apoAII expression caused by fibrates in HepG2 cells. After fenofibric acid treatment, we show a parallel increase in apoAII and core protein secretion, this effect being abolished by brefeldin A. Our study identifies apoAII as one of the cellular targets for HCV core protein. We also show that the intervention of fenofibric acid in cellular lipid metabolism directly affects the expression pattern of HCV core protein.

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