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

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 BRF (BAZ2B-Associated Remodeling Factor) ISWI chromatin remodeling complexes. ShRNAs-mediated silencing of BAZ2B or its inactivation with the BAZ2B-BRD inhibitor GSK-2801 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.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Hepatocyte, Liver

DISEASE(S): Hepatitis D

SUBMITTER: Paul Dény  

LAB HEAD: Pr. Massimo Levrero

PROVIDER: PXD016880 | Pride | 2020-05-27

REPOSITORIES: Pride