Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication
- 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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| Author: | Natali Abeywickrama-Samarakoon, Jean-Claude Cortay, Camille Sureau, Susanne MüllerORCiD, Dulce Alfaiate, Francesca GuerrieriORCiD, Apirat ChaikuadORCiD, Martin SchröderORCiDGND, Philippe Merle, Massimo Levrero, Paul DényORCiD |
|---|---|
| URN: | urn:nbn:de:hebis:30:3-531126 |
| DOI: | https://doi.org/10.1038/s41467-020-14299-9 |
| ISSN: | 2041-1723 |
| Pubmed Id: | https://pubmed.ncbi.nlm.nih.gov/31964889 |
| Parent Title (English): | Nature Communications |
| Publisher: | Nature Publishing Group UK |
| Place of publication: | [London] |
| Document Type: | Article |
| Language: | English |
| Year of Completion: | 2020 |
| Date of first Publication: | 2020/01/21 |
| Publishing Institution: | Universitätsbibliothek Johann Christian Senckenberg |
| Release Date: | 2020/03/16 |
| Tag: | Microbiology; Pathogenesis |
| Volume: | 11 |
| Issue: | 1, Art. 419 |
| Page Number: | 13 |
| First Page: | 1 |
| Last Page: | 13 |
| Note: | Open Access: This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/. |
| HeBIS-PPN: | 463910214 |
| Institutes: | Biochemie, Chemie und Pharmazie / Pharmazie |
| Exzellenzcluster / Exzellenzcluster Makromolekulare Komplexe | |
| Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
| Sammlungen: | Universitätspublikationen |
| Licence (German): |  Creative Commons - Namensnennung 4.0 |
