Effect of viral DNA methylation on expression of hepatitis B virus proteins depends on the virus genotype
- 1 August 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Virus Genes
- Vol. 56 (4), 439-447
- https://doi.org/10.1007/s11262-020-01761-5
Abstract
The frequency of HBV genomic methylation in the liver was reported to vary among patients, but the detailed mechanism is still unknown. In this study, the effects of HBV genome methylation on HBV replication were investigated in vitro. A total of 6 plasmids containing 1.24-fold the HBV genome of different genotypes (subgenotypes A1, A2, B1, and C2) were purified after in vitro methylation with CpG methyltransferase (M.SssI) and transfected into HepG2 cells. In genotype B and C strains, methylation markedly decreased the amount of hepatitis B e antigen (HBeAg) in the culture supernatant. A reduction of hepatitis B surface antigen (HBsAg) was found in some HBV strains but the reduction was smaller than that of HBeAg. There was no significant difference in particle-associated HBV DNA in the culture supernatant. These findings suggest that HBV genomic methylation might be involved in the HBeAg decline in genotype B and C, in part, and that the reduction of HBsAg was less than that of HBeAg. In conclusion, this study showed that the effect of HBV genomic methylation differs among HBV genotypes, suggesting a potential explanation for the different clinical outcomes of genotypes A, B, and C.Funding Information
- Japan Society for the Promotion of Science (19K08385)
This publication has 33 references indexed in Scilit:
- DNA methylation directly silences genes with non-CpG island promoters and establishes a nucleosome occupied promoterHuman Molecular Genetics, 2011
- Hepatitis B viral DNA is methylated in liver tissuesJournal of Viral Hepatitis, 2007
- A Genotype-Independent Real-Time PCR Assay for Quantification of Hepatitis B Virus DNAJournal of Clinical Microbiology, 2007
- Spatial and chronological differences in hepatitis B virus genotypes from patients with acute hepatitis B in JapanHepatology Research, 2006
- Influence of hepatitis B virus genotypes on the intra- and extracellular expression of viral DNA and antigensHepatology, 2006
- Persistence of acute infection with hepatitis B virus genotype A and treatment in JapanJournal of Medical Virology, 2005
- Sex- and Age-Specific Carriers of Hepatitis B and C Viruses in Japan Estimated by the Prevalence in the 3,485,648 First-Time Blood Donors during 1995–2000Intervirology, 2004
- Different hepatitis b virus genotypes are associated with different mutations in the core promoter and precore regions during hepatitis B e antigen seroconversionHepatology, 1999
- MUTATION PREVENTING FORMATION OF HEPATITIS B e ANTIGEN IN PATIENTS WITH CHRONIC HEPATITIS B INFECTIONThe Lancet, 1989
- Typing Hepatitis B Virus by Homology in Nucleotide Sequence: Comparison of Surface Antigen SubtypesJournal of General Virology, 1988