Role of hepatitis B core protein in HBV transcription and recruitment of histone acetyltransferases to cccDNA minichromosome

Antiviral Research
Chun Kong ChongDanny Ka-Ho Wong

Abstract

The hepatitis B core protein (HBc) has been suggested to interact with covalently closed circular DNA (cccDNA) and regulate hepatitis B virus (HBV) transcription. However, direct evidence is lacking. We aimed to identify the specific HBc region(s) responsible for transcription regulation and its interaction with cccDNA. Seventeen mutants with mutations at the four arginine-rich clusters of the HBc carboxyl-terminal domain (CTD) were created. The effect of HBc mutations on the levels of HBV DNA, RNA, and hepatitis B surface antigen (HBsAg) were measured. The association of cccDNA with mutant HBc and histone acetyltransferases (HATs) was assessed by chromatin immunoprecipitation (ChIP). Compared with wild-type HBc, HBc mutants with mutations in clusters III and IV resulted in a significant reduction in HBV RNA levels (all P < 0.05). HBc arginine clusters III and IV mutants also had a significantly lower levels of intracellular HBV DNA (<5% of wild-type; P < 0.001) and HBsAg (<10% of wild-type; P < 0.0001). cccDNA-ChIP assay demonstrated that HBc clusters III and IV mutants had a smaller degree of association with cccDNA (P < 0.001). In the HBc mutants, the association between HATs with cccDNA were reduced. In conclusion, HBc-CTD ...Continue Reading

Citations

Oct 27, 2017·Expert Opinion on Therapeutic Targets·Lung-Yi MakMan Fung Yuen
Aug 29, 2019·Nature Reviews. Drug Discovery·Gregory C FanningAntonio Bertoletti
Oct 15, 2019·Journal of Clinical and Translational Hepatology·Anjing ZhuXiaoqiong Duan
Nov 20, 2019·The Journal of Infectious Diseases·Ashwin BalagopalChloe L Thio
Jun 8, 2017·Viruses·Xiaoling LiNingshao Xia
Nov 6, 2020·Infection and Drug Resistance·Maura Dandri, Joerg Petersen
Jun 25, 2021·World Journal of Gastroenterology : WJG·Prashika SinghKristie Bloom
Aug 11, 2021·Viruses·Bingqian Qu, Richard J P Brown
Dec 13, 2018·ACS Infectious Diseases·Ana Maria Ortega-PrietoMarcus Dorner

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