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 Transcrip- Tional 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, Methyla- Tion-Specific Pcr and Bisulfite Sequencing. Ifn-α Suppressed Hbv Dna and Rna Transcripts, But Methylation Profiles Were Similar Between The Control and fnI-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.