Role of epigenetic modification in interferon treatment of hepatitis B virus infection

Abstract

Human hepatitis B virus (HBV) is a small, enveloped DNA virus that causes acute and chronic hepatitis. Chronic hepatitis B (CHB) is associated with hepatocellular carcinoma pathogenesis. Interferons (IFNs) have been used for the treatment of CHB for a long time, with advantages including less treatment duration and sustained virological response. Presently, various evidence suggests that epigenetic modification of the viral covalently closed circular DNA (cccDNA) and the host genome is crucial for the regulation of viral activity. This modification includes histone acetylation, DNA methylation, N6-methyladenosine, and non-coding RNA modification. IFN treatment for CHB can stimulate multiple IFN-stimulated genes for inhibiting virus replication. IFNs can also affect the HBV life cycle through epigenetic modulation. In this review, we summarized the different mechanisms through which IFN-α inhibits HBV replication, including epigenetic regulation. Moreover, the mechanisms underlying IFN activity are discussed, which indicated its potential as a novel treatment for CHB. It is proposed that epigenetic changes such as histone acetylation, DNA methylation, m6A methylation could be the targets of IFN, which may offer a novel approach to HBV treatment.

Characteristic of molecular subtypes based on PANoptosis-related genes and experimental verification of hepatocellular carcinoma

“…IFN-γ is approved as a cytokine for several cancer species and has been shown to induce apoptosis of HCC cells [ 51 ]. IFN was also used for chronic hepatitis B [ 52 ]. As a critical risk factor for HCC, whether the therapeutic effect of hepatitis B virus infection is affected by PANoptosis level needs to be further demonstrated.…”

Overview of the immunological mechanisms in hepatitis B virus reactivation: Implications for disease progression and management strategies

“…Furthermore, Wang et al [ 30 ] revealed that HBsAg, hepatitis B e antigen (HBeAg), hepatitis B x, and HBV virions possess the capability to impede the synthesis of IFN-β, hence reducing mitochondrial anti-viral signaling (MAVS) and disrupt the link between MAVS and RIG-I. The study conducted by Yang et al [ 31 ] demonstrates that IFN-I can directly reduce HBV infection by activating IFN-stimulated genes upon binding to the IFN receptor. This activation subsequently impedes viral replication.…”

“…This activation subsequently impedes viral replication. Nevertheless, HBV can substantially impair the signal transduction triggered by IFN-I and attenuate the immunological responses facilitated by IFN-I[ 31 ].…”

T cell-derived exosomes in tumor immune modulation and immunotherapy

“…Additionally, CD4 + T cell-derived exosomes play an important role in B cell responses in vitro , which significantly promotes B cell activation, proliferation, and antibody production ( 45 ). It is well known that hepatitis B virus is the main cause of hepatocellular carcinoma ( 46 – 48 ), and the synergistic effect of CD4 + T cell-derived exosomes on HBsAb may contribute to the inhibition of hepatocellular carcinoma. Further research is required to confirm this hypothesis.…”