Hepatitis B virus X protein modulates remodelling of minichromosomes related to hepatitis B virus replication in HepG2 cells.

Hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is organised into minichromosomes by histone and non-histone proteins. Remodelling of minichromosomes is crucial for the regulation of HBV replication, which is dependent on the presence of the hepatitis B virus X protein (HBx). However, the mechanisms of HBx-dependent HBV replication remain obscure. The objective of this study was to investigate the mechanism of HBx-dependent HBV replication through the pathway of chromatin remodelling. The role of HBx was investigated by transfecting human HepG2 cells with the linear full-length HBV genome (wild-type) or HBx-deficient mutant HBV DNA (HBx mutant). Our results showed that although the formation of cccDNA was not affected by HBx, HBV replication, transcription and antigen secretion were all significantly reduced, resulting from the absence of HBx. The acetylation, mono-methylation and phosphorylation of cccDNA-bound histone H3 were associated with HBV replication. In addition, the levels of cccDNA-bound methylated, phosphorylated and acetylated histone H3 decreased sharply in HBx mutant HBV DNA. HBx modulated not only the status of acetylation but also the methylation and phosphorylation of histone H3 bound to the cccDNA during HBV replication in HepG2 cells. These findings suggest that HBx plays an important role in modulating the remodelling of minichromosomes related to HBV replication and it may regulate viral replication through the pathway of chromatin remodelling.