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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 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.
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Submitted on : Thursday, February 27, 2020 - 4:41:49 PM
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Natali Abeywickrama-Samarakoon, Jean-Claude Cortay, Camille Sureau, Susanne Müller, Dulce Alfaiate, et al.. Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication. Nature Communications, Nature Publishing Group, 2020, 11 (1), pp.419. ⟨10.1038/s41467-020-14299-9⟩. ⟨inserm-02493313⟩

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