Regulatory mechanisms for HBV replication

Hepatitis B virus (HBV) is one of the smallest enveloped DNA viruses and infects more than 350 million people worldwide. HBV infection causes acute and chronic hepatitis, and is one of the major causes of cirrhosis and hepatocellular carcinoma. Currently available therapies can achieve viral suppression, but not termination of HBV infection. HBV replicates its genome via an RNA intermediate in infected hepatocytes. Complex virus-host interactions ensure that the virus is able to fulfill its replication requirements while successfully evading antiviral innate immune responses. An in-depth understanding of the molecular mechanisms regulating HBV replication is necessary for designing more effective therapeutic strategies, which would in turn improve the management of patients with chronic HBV infection and eventually help achieve viral eradication. The regulation of HBV transcription is a critical step in the viral life cycle and has been extensively investigated. The replication of HBV can also be regulated by other mechanisms, including regulation of the stability of HBV transcripts and viral protein, regulation of capsid assembly, and regulation of HBV DNA synthesis. In addition, recent studies have revealed that HBV replication is subject to epigenetic regulation by several mechanisms, including DNA methylation, histone acetylation, and microRNAs (miRNAs). This review focuses on the molecular mechanisms underlying the regulation of HBV replication, with special emphasis on the epigenetic mechanisms.