Induction of hepatitis B virus core gene in human cells by cytosine demethylation in the promoter.

A recombinant human cell line constructed by transfection of epithelial cells with a plasmid containing the hepatitis B virus core gene (HBc) was used to study the regulation of HBc gene expression. Methylation of a single Hpa II site 280 base pairs upstream from the structural gene was found to regulate the expression of the core gene. Expression increased in cells treated with 5'-azacytidine as a result of cytosine demethylation at this site, and there was a fivefold increase in the number of HBc gene transcripts in total cellular messenger RNA. The varied life cycle of hepatitis B virus in disease such as viral hepatitis and liver cancer may therefore be attributable to the site-specific regulation of the gene involved in replication of the viral DNA and to the cytophathic effects elicited by this gene in human cells.