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Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication

Author

Listed:
  • Natali Abeywickrama-Samarakoon

    (INSERM, U1052 UMR CNRS 5286, Cancer Research Center of Lyon (CRCL))

  • Jean-Claude Cortay

    (INSERM, U1052 UMR CNRS 5286, Cancer Research Center of Lyon (CRCL))

  • Camille Sureau

    (Laboratoire de Virologie Moléculaire, INSERM U1134, Institut National de la Transfusion Sanguine)

  • Susanne Müller

    (Structural Genomics Consortium, Buchmann Institute for Molecular Life Sciences, Johann Wolfgang Goethe-University)

  • Dulce Alfaiate

    (INSERM, U1052 UMR CNRS 5286, Cancer Research Center of Lyon (CRCL)
    Université de Genève
    Hôpital de la Croix Rousse, Hospices Civils de Lyon and Université Lyon I)

  • Francesca Guerrieri

    (INSERM, U1052 UMR CNRS 5286, Cancer Research Center of Lyon (CRCL)
    Sapienza University)

  • Apirat Chaikuad

    (Structural Genomics Consortium, Buchmann Institute for Molecular Life Sciences, Johann Wolfgang Goethe-University)

  • Martin Schröder

    (Structural Genomics Consortium, Buchmann Institute for Molecular Life Sciences, Johann Wolfgang Goethe-University)

  • Philippe Merle

    (INSERM, U1052 UMR CNRS 5286, Cancer Research Center of Lyon (CRCL)
    Hôpital de la Croix Rousse, Hospices Civils de Lyon and Université Lyon I)

  • Massimo Levrero

    (INSERM, U1052 UMR CNRS 5286, Cancer Research Center of Lyon (CRCL)
    Sapienza University
    Hôpital de la Croix Rousse, Hospices Civils de Lyon and Université Lyon I)

  • Paul Dény

    (INSERM, U1052 UMR CNRS 5286, Cancer Research Center of Lyon (CRCL)
    Laboratoire de Microbiologie Clinique, Groupe des Hôpitaux Universitaires de Paris - Seine Saint Denis, UFR Santé Médecine, Biologie Humaine, Université Paris 13)

Abstract

Hepatitis Delta virus (HDV) is a satellite of Hepatitis B virus with a single-stranded circular RNA genome. HDV RNA genome synthesis is carried out in infected cells by cellular RNA polymerases with the assistance of the small hepatitis delta antigen (S-HDAg). Here we show that S-HDAg binds the bromodomain (BRD) adjacent to zinc finger domain 2B (BAZ2B) protein, a regulatory subunit of BAZ2B-associated remodeling factor (BRF) ISWI chromatin remodeling complexes. shRNA-mediated silencing of BAZ2B or its inactivation with the BAZ2B BRD inhibitor GSK2801 impairs HDV replication in HDV-infected human hepatocytes. S-HDAg contains a short linear interacting motif (SLiM) KacXXR, similar to the one recognized by BAZ2B BRD in histone H3. We found that the integrity of the S-HDAg SLiM sequence is required for S-HDAg interaction with BAZ2B BRD and for HDV RNA replication. Our results suggest that S-HDAg uses a histone mimicry strategy to co-activate the RNA polymerase II-dependent synthesis of HDV RNA and sustain HDV replication.

Suggested Citation

  • Natali Abeywickrama-Samarakoon & Jean-Claude Cortay & Camille Sureau & Susanne Müller & Dulce Alfaiate & Francesca Guerrieri & Apirat Chaikuad & Martin Schröder & Philippe Merle & Massimo Levrero & Pa, 2020. "Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
  • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14299-9
    DOI: 10.1038/s41467-020-14299-9
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