Hepatitis Delta Virus Histone Mimicry Drives the Recruitment of Chromatin Remodelers for Viral RNA Replication

Overview

Journal Nat Commun

Specialty Biology

Date 2020 Jan 23

PMID 31964889

Citations 14

Authors

Natali Abeywickrama-Samarakoon

Jean-Claude Cortay

Camille Sureau

Susanne Muller

Dulce Alfaiate

Francesca Guerrieri

Apirat Chaikuad

Martin Schroder

Philippe Merle

Massimo Levrero

Paul Deny

Affiliations

Soon will be listed here.

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.

Citing Articles

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