Hepatitis C Virus Core Protein Induces Lipid Droplet Redistribution in a Microtubule- and Dynein-Dependent Manner

Authors

  • Steeve Boulant,

    Corresponding author
    1. MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK
    2. Current address: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA
      *Steeve Boulant, steeve_boulant@hms.harvard.edu
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  • Mark W. Douglas,

    1. MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK
    2. Current address: Storr Liver Unit, Westmead Millennium Institute, Westmead NSW 2145, Australia
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  • Laura Moody,

    1. MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK
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  • Agata Budkowska,

    1. Unité Hépacivirus Institut Pasteur, 25/28 Rue du Dr Roux, 75724 Paris Cedex 15, France
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  • Paul Targett-Adams,

    1. MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK
    2. Current address: Pfizer PGRD, Sandwich Laboratories IPC: 424, Sandwich, Kent CT13 9NJ, UK
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  • John McLauchlan

    1. MRC Virology Unit, Institute of Virology, Church Street, Glasgow G11 5JR, UK
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*Steeve Boulant, steeve_boulant@hms.harvard.edu

Abstract

Attachment of hepatitis C virus (HCV) core protein to lipid droplets (LDs) is linked to release of infectious progeny from infected cells. Core progressively coats the entire LD surface from a unique site on the organelle, and this process coincides with LD aggregation around the nucleus. We demonstrate that LD redistribution requires only core protein and is accompanied by reduced abundance of adipocyte differentiation-related protein (ADRP) on LD surfaces. Using small hairpin RNA technology, we show that knock down of ADRP has a similar phenotypic effect on LD redistribution. Hence, ADRP is crucial to maintain a disperse intracellular distribution of LDs. From additional experimental evidence, LDs are associated with microtubules and aggregate principally around the microtubule-organizing centre in HCV-infected cells. Disrupting the microtubule network or microinjecting anti-dynein antibody prevented core-mediated LD redistribution. Moreover, microtubule disruption reduced virus titres, implicating transport networks in virus assembly and release. We propose that the presence of core on LDs favours their movement towards the nucleus, possibly to increase the probability of interaction between sites of HCV RNA replication and virion assembly.

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