Hepatitis Delta Virus histone mimicry drives the recruitment of chromatin remodelers for viral RNA replication.
Nat Commun
; 11(1): 419, 2020 01 21.
Article
em En
| MEDLINE
| ID: mdl-31964889
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.
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Vírus Delta da Hepatite
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Proteínas
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Mimetismo Molecular
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Antígenos da Hepatite delta
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Montagem e Desmontagem da Cromatina
Idioma:
En
Ano de publicação:
2020
Tipo de documento:
Article