Silencing hepatitis B virus covalently closed circular DNA: The potential of an epigenetic therapy approach

作     者：Prashika Singh Dylan Kairuz Patrick Arbuthnot Kristie Bloom 

作者机构：Wits/SAMRC Antiviral Gene Therapy Research UnitSchool of PathologyUniversity of the WitwatersrandJohannesburg 2050GautengSouth Africa 

出 版 物：《World Journal of Gastroenterology》 (世界胃肠病学杂志（英文版）)

年 卷 期：2021年第27卷第23期

页      面：3182-3207页

核心收录：

学科分类：1004[医学-公共卫生与预防医学(可授医学、理学学位)] 100401[医学-流行病与卫生统计学] 10[医学] 

基　　金：UK Research and Innovation  UKRI  (104824) 

主　　题：Chronic hepatitis B virus Epigenetic gene silencing Functional cure Hepatocellular carcinoma Hepatitis B surface antigen 

摘      要：Global prophylactic vaccination programmes have helped to curb new hepatitis B virus(HBV)***,it is estimated that nearly 300 million people are chronically infected and have a high risk of developing hepatocellular *** such,HBV remains a serious health priority and the development of novel curative therapeutics is urgently *** HBV infection has been attributed to the persistence of the covalently closed circular DNA(cccDNA)which establishes itself as a minichromosome in the nucleus of *** the viral transcription intermediate,the cccDNA is responsible for producing new virions and perpetuating *** is dependent on various host factors for cccDNA formation and the minichromosome is amenable to epigenetic *** HBV proteins,X(HBx)and core(HBc)promote viral replication by modulating the cccDNA epigenome and regulating host cell *** includes viral and host gene expression,chromatin remodeling,DNA methylation,the antiviral immune response,apoptosis,and *** of the cccDNA minichromosome would result in a sterilizing cure;however,this may be difficult to *** therapies could permanently silence the cccDNA minichromosome and promote a functional *** review explores the cccDNA epigenome,how host and viral factors influence transcription,and the recent epigenetic therapies and epigenome engineering approaches that have been described.