Resumen

Background and aim. The HBV covalently closed circular DNA (cccDNA) is organized into a minichromosome in the nuclei of infected hepatocytes through interactions with histone and nonhistone proteins. Retinoid X receptor á (RXRá), a liver-enriched nuclear receptor, participates in regulation of HBV replication and transcription through modulation of HBV enhancer 1 and core promoter activity. Material and methods. This study investigated RXRá involvement in HBV cccDNA epigenetic modifications. Quantitative cccDNA chromatin immunoprecipitation (ChIP) was applied to study the recruitment of RXRá, histones, and chromatin-modifying enzymes to HBV minichromosome in HepG2 cells after transfection of the linear HBV genome. Results. RXRá was found to directly bind to HBV cccDNA; recruitment of RXRá to HBV mini-chromosome paralleled HBV replication, histone recruitment, and histone acetylation in HBVcccDNA. Moreover, RXRá overexpression or knock-down significantly increased or impaired the recruitment of the p300 acetyltransferase to cccDNAminichromosome. Conclusions. Our results confirmed the regulation of RXRá on HBV replication in vitro and demonstrated the modulation of RXRá on HBV cccDNA epigenetics. These findings provide a profound theoretical and experimental basis for late-model antiviral treatment acting on the HBV cccDNA and minichromosome.

Palabras clave: Hepatitis B virus covalently closed circular DNA (cccDNA) retinoid X receptor á viral minichromosome remodeling.

2017-12-14   |   108 visitas   |   Evalua este artículo 0 valoraciones

Vol. 16 Núm.4. Julio-Agosto 2017 Pags. 501-509 Ann Hepatol 2017; 16(4)