Augmented epigenetic repression of hepatitis B virus covalently closed circular DNA by interferon-α and small-interfering RNA synergy.

ABSTRACT: The persistence of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) is a key obstacle for HBV cure. This study aims to comprehensively assess the effect of interferon (IFN) and small-interfering RNA (siRNA) combination on the cccDNA minichromosome. Utilizing both cell and mouse cccDNA models, we compared the inhibitory effects of IFNα, siRNA, and their combination on cccDNA activity and assessed its epigenetic state. IFNα2 treatment alone reduced HBV RNAs, HBeAg, and HBsAg levels by approximately 50%, accompanied by a low-level reconstitution of SMC5/6-a chromatin modulator that restricts cccDNA transcription. HBx-targeting siRNA (siHBx) achieved significant suppression of viral antigens and reconstitution of SMC5/6, but this effect could be reversed by the deacetylase inhib

SUBMITTER: Hu K 

PROVIDER: S-EPMC11633095 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature