RESEARCH ARTICLE Genomic Methylation Inhibits Expression of Hepatitis B Virus Envelope Protein in Transgenic Mice: A Non-Infectious Mouse Model to Study Silencing of HBV Surface Antigen Genes

Objective The Hepatitis B virus genome persists in the nucleus of virus infected hepatocytes where it serves as template for viral mRNA synthesis. Epigenetic modifications, including methyla-tion of the CpG islands contribute to the regulation of viral gene expression. The present study investigates the effects of spontaneous age dependent loss of hepatitis B surface pro-tein- (HBs) expression due to HBV-genome specific methylation as well as its proximate positive effects in HBs transgenic mice. Methods Liver and serum of HBs transgenic mice aged 5–33 weeks were analyzed by Western blot, immunohistochemistry, serum analysis, PCR, and qRT-PCR. Results From the third month of age hepatic loss of HBs was observed in 20 % of transgenic mice. The size of HBs-free area and the relative number of animals with these effects increased with age and struck about 55 % of animals aged 33 weeks. Loss of HBs-expression wa