• Open Access

Hepatoma polarization limits CD81 and hepatitis C virus dynamics

Authors

  • H. J. Harris,

    1. School of Immunity and Infection, University of Birmingham, Birmingham, UK
    2. NIHR Centre for Liver Disease, University of Birmingham, Birmingham, UK
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  • C. Clerte,

    1. Unité 1054, Inserm, Montpellier, France
    2. Centre de Biochimie Structurale, Université de Montpellier, CNRS, UMR 5048, Montpellier, France
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  • M. J. Farquhar,

    1. School of Immunity and Infection, University of Birmingham, Birmingham, UK
    2. NIHR Centre for Liver Disease, University of Birmingham, Birmingham, UK
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  • M. Goodall,

    1. School of Immunity and Infection, University of Birmingham, Birmingham, UK
    2. NIHR Centre for Liver Disease, University of Birmingham, Birmingham, UK
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  • K. Hu,

    1. School of Immunity and Infection, University of Birmingham, Birmingham, UK
    2. NIHR Centre for Liver Disease, University of Birmingham, Birmingham, UK
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  • P. Rassam,

    1. Unité 1054, Inserm, Montpellier, France
    2. Centre de Biochimie Structurale, Université de Montpellier, CNRS, UMR 5048, Montpellier, France
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  • P. Dosset,

    1. Unité 1054, Inserm, Montpellier, France
    2. Centre de Biochimie Structurale, Université de Montpellier, CNRS, UMR 5048, Montpellier, France
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  • G. K. Wilson,

    1. School of Immunity and Infection, University of Birmingham, Birmingham, UK
    2. NIHR Centre for Liver Disease, University of Birmingham, Birmingham, UK
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  • P. Balfe,

    1. School of Immunity and Infection, University of Birmingham, Birmingham, UK
    2. NIHR Centre for Liver Disease, University of Birmingham, Birmingham, UK
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  • S. C. IJzendoorn,

    1. Department of Cell Biology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • P. E. Milhiet,

    1. Unité 1054, Inserm, Montpellier, France
    2. Centre de Biochimie Structurale, Université de Montpellier, CNRS, UMR 5048, Montpellier, France
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    • These authors shared senior authorship.
  • J. A. McKeating

    Corresponding author
    1. NIHR Centre for Liver Disease, University of Birmingham, Birmingham, UK
    2. NIHR Liver Biomedical Research Unit, University of Birmingham, Birmingham, UK
    • School of Immunity and Infection, University of Birmingham, Birmingham, UK
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    • These authors shared senior authorship.

For correspondence. E-mail j.a.mckeating@bham.ac.uk; Tel. (+44) 121 414 8173; Fax (+44) 121 414 3599.

Summary

Many viruses target the polarized epithelial apex during host invasion. In contrast, hepatitis C virus (HCV) engages receptors at the basal surface of hepatocytes in the polarized liver parenchyma. Hepatocyte polarization limits HCV entry by undefined mechanism(s). Given the recent reports highlighting a role for receptor mobility in pathogen entry, we studied the effect(s) of hepatocyte polarization on viral receptor and HCV pseudoparticle (HCVpp) dynamics using real-time fluorescence recovery after photobleaching and single particle tracking. Hepatoma polarization reduced CD81 and HCVpp dynamics at the basal membrane. Since cell polarization is accompanied by changes in the actin cytoskeleton and CD81 links to actin via its C-terminus, we studied the dynamics of a mutant CD81 lacking a C-terminal tail (CD81ΔC) and its effect(s) on HCVpp mobility and infection. CD81ΔC showed an increased frequency of confined trajectories and a reduction of Brownian diffusing molecules compared to wild-type protein in non-polarized cells. However, these changes were notobserved in polarized cells. HCVpp showed a significant reduction in Brownian diffusion and infection of CD81ΔC expressing non-polarized cells. In summary, these data highlight the dynamic nature of CD81 and demonstrate a role for CD81 lateral diffusion to regulate HCV infection in a polarization-dependent manner.

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