Methylation profile of hepatitis B virus is not influenced by interferon α in human liver cancer cells

Abstract

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.

Evaluation of the Relationships between Intestinal Regional Lymph Nodes and Immune Responses in Viral Infections in Children

“…Moreover, patients prescribed steroids were excluded because steroid use is associated with low IgA levels [ 25 ]. Cases of hepatitis were also excluded because they may be prescribed IFN as a therapeutic agent [ 26 ]. Blood IFNβ levels below the detection limit were found in approximately 80% of cases in each of the viral infection, bacterial infection, and non-infection groups.…”

Silicon Nanowires Length and Numbers Dependence on Sensitivity of the Field-Effect Transistor Sensor for Hepatitis B Virus Surface Antigen Detection

“…The most commonly used diagnostic method for HBV is the enzyme-linked immunosorbent assay. However, this method is complex, requires a large number of samples, and has inadequate sensitivity [ 33 ]. Thus, this study used polycrystalline silicon (poly-Si) NWFET sensors with nanowires of various sizes to detect HBV.…”