Epigenetic regulation of covalently closed circular DNA minichromosome in hepatitis B virus infection

Hepatitis B is caused by hepatitis B virus (HBV), and persistent HBV infection is a global public health problem, with 257 million people as HBV chronic carriers. Viral covalently closed circular DNA (cccDNA) is a key factor to establish persistent infection in infected hepatocytes. Current antiviral therapies have no direct impact on pre-existing cccDNA reservoir, which can be assembled into minichromosome by hijacking host factors. Understanding the mechanisms of epigenetic regulation in cccDNA minichromosome is crucial to develop new therapy on cccDNA, an attractive target for HBV cure. This review summarizes the current advances in epigenetic regulation of cccDNA minichromosome, which might provide clues to novel druggable targets to cure hepatitis B by either silencing or eliminating cccDNA reservoir.