Retinoid X Receptor α-Dependent HBV Minichromosome Remodeling and Viral Replication
Journal Title: Annals of Hepatology - Year 2017, Vol 16, Issue 4
Abstract
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 ? (RXR?), 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 RXR? involvement in HBV cccDNA epigenetic modifications. Quantitative cccDNA chromatin immunoprecipitation (ChIP) was applied to study the recruitment of RXR?, histones, and chromatin-modifying enzymes to HBV minichromosome in HepG2 cells after transfection of the linear HBV genome. Results. RXR? Was found to directly bind to HBV cccDNA; recruitment of RXR? to HBV mini-chromosome paralleled HBV replication, histone recruitment, and histone acetylation in HBVcccDNA. Moreover, RXR? overexpression or knock-down significantly increased or impaired the recruitment of the p300 acetyltransferase to cccDNAminichromosome. Conclusions. Our results confirmed the regulation of RXR? on HBV replication in vitro and demonstrated the modulation of RXR? 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.
Authors and Affiliations
Yan Zhang, Song He, Jin-Jun Guo, Hong Peng, Jia-Hao Fan, Qing-Ling Li
Keywords
Related Articles
- EP ID EP189417
- DOI 10.5604/01.3001.0010.0275
- Views 115
- Downloads 0
Hepatocellular carcinoma that arose from primary Sjögren’s syndrome
Hepatocellular carcinoma (HCC) typically originates from HBV or HCV associated liver cirrhosis. Primary Sjögren’s syndrome (pSS) is a kind of autoimmune disease. A sixty-two year old female patient with mild liver damage...
Hepatocellular adenoma: different entities for a single lesion
Treatment of chronic HBV infection in developing countries
Due to virological, host and socio-economic factors, the clinical presentation and treatment of chronic hepatitis B (CHB) differs between developing and developed countries and may differ between one low-income country...
Shortened therapy for genotype 1 hepatitis C virus. The final answer?
Background & Aims. In hepatitis C virus genotype 1 (HCV-1) patients with a rapid viral decline within the first month of therapy, a 24-week course of pegylated interferon (PEG-IFN) alpha and ribavirin treatme...
Search for Genetic Modifiers of PSC: Time to Increase the Number of Needles in the Haystack
Primary sclerosing cholangitis (PSC) belongs to the most obscure liver diseases. Patients with progressive PSC require liver transplantation as only therapeutic option. Previously several HLA- and non-HLA-associated PSC...