Histone deacetylases and acetylated histone H3 are involved in the process of hepatitis B virus DNA replication.
AIMS
The aim of this study was to investigate the relationship between anti-HBV treatment and the regulation of HDACs during HBV DNA replication.


METHODS
HDAC activities and HBV DNA levels in CHB patients' sera were measured and correlation analysis was made. The changes of HDAC2, HDAC6, AH3 and histone H3 levels in normal control and 4 CHB patient liver tissue samples before and after antiviral treatment were examined. The HDAC inhibitor, TSA, anti-HBV agents, ETV and IFN-α were used to stimulate HepG2.2.15 cells. The levels of HBV DNA, pgRNA in supernatants, and cccDNA in the cells were determined by PCR. The HDAC activity, HDAC6, HDAC2, AH3 and H3 protein levels in cells were tested at days 3, 6, and 9 after treatments.


KEY FINDINGS
HDAC activity was positively correlated with HBV DNA in the HBV patients' sera. The levels of HDAC2, HDAC6 and AH3 were notably decreased after antiviral treatment. When compared with antiviral treatment group, the normal liver tissue showed obviously decreased HDAC2, HDAC6 and AH3 protein levels. In vitro study, the level of HBV DNA, the HDAC activity, and the HDAC2, HDAC6 and AH3 protein levels decreased in the ETV, IFN-α and TSA groups compared with the control group. The pgRNA level in supernatants was declined in the IFN-α group and increased in the ETV and TSA groups. cccDNA expression was suppressed by IFN-α.


SIGNIFICANCE
The changes of HBV replicative products during antiviral treatment are associated with histone deacetylation. Acetylated histone H3 is involved in the process of hepatitis B virus DNA replication.
['Zhang|Di|D|', 'Wang|Yao|Y|', 'Zhang|Hai-Yue|HY|', 'Jiao|Fang-Zhou|FZ|', 'Zhang|Wen-Bin|WB|', 'Wang|Lu-Wen|LW|', 'Zhang|Hong|H|', 'Gong|Zuo-Jiong|ZJ|']
D000328:Adult D000998:Antiviral Agents D018929:Cell Culture Techniques D004261:DNA Replication D004279:DNA, Viral D005260:Female D056945:Hep G2 Cells D006515:Hepatitis B virus D019694:Hepatitis B, Chronic D056572:Histone Deacetylase Inhibitors D006655:Histone Deacetylases D006657:Histones D006801:Humans D008099:Liver D008297:Male D008875:Middle Aged D014779:Virus Replication
Histone deacetylases Acetylated histone H3 Replication HBV DNA