Methylation profile of hepatitis B virus is not influenced by interferon α in human liver cancer cells
- In Young Moon
- Jin-Wook Kim
Affiliations: Department of Medicine, Seoul National University Bundang Hospital, Seongnam, Gyeonggi 13620, Republic of Korea
- Published online on: August 10, 2021 https://doi.org/10.3892/mmr.2021.12354
Copyright: © Moon
et al. This is an open access article distributed under the
terms of Creative
Commons Attribution License.
Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
This article is mentioned in:
Interferon (IFN) α is used for the treatment of chronic hepatitis B virus (HBV) infection, but the molecular mechanisms underlying its antiviral effect have not been fully elucidated. Epigenetic modifications regulate the transcriptional activity of covalently closed circular DNA (cccDNA) in cells with chronic HBV infection. IFN‑α has been shown to modify cccDNA‑bound histones, but it is not known whether the anti‑HBV effect of IFN‑α involves methylation of cccDNA. The present study aimed to determine whether IFN‑α induced methylation of HBV cccDNA in a cell‑based model in which HepG2 cells were directly infected with wild‑type HBV virions. Methylation status of HBV cccDNA was assessed using global DNA methylation ELISA assay, methylation‑specific PCR and bisulfite sequencing. IFN‑α suppressed HBV DNA and RNA transcripts, but methylation profiles were similar between the control and IFN‑α treated groups. Chromatin immunoprecipitation results revealed binding of DNA methyltransferases (DNMT) 3A and DNMT3B to HBV cccDNA and treatment with IFN‑α suppressed the recruitment of DNMT3B to cccDNA. Taken together, these results suggest that IFN‑α does not induce methylation of HBV cccDNA. Therefore, it was concluded that methylation is unlikely to contribute to the anti‑HBV effect of IFN‑α in HepG2 cells, and that alternative mechanisms need to be sought to enhance cccDNA methylation as a novel therapy against HBV.