ArticleActa pharmacologica Sinica2022
IFN-α inhibits HBV transcription and replication by promoting HDAC3-mediated de-2-hydroxyisobutyrylation of histone H4K8 on HBV cccDNA minichromosome in liver.
Article in Acta pharmacologica Sinica, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 24 citations in OpenAlex.
- The histone deacetylase family in health and disease.Signal transduction and targeted therapy · 2026Review
- qHBsAg Trajectories with Peg-IFNα-2b Add-on Therapy in Nucleos(t)ide Analog-experienced HBeAg-positive Chronic Hepatitis B.Journal of clinical and translational hepatology · 2026Article
- Novel protein acylations in Alzheimer's disease: Molecular, mechanisms, biological significance, and diagnostic and therapeutic potentials.Journal of advanced research · 2026Review
- [Comparison of antiviral efficacy of nucleos(t)ide analogue monotherapy and its combination with interferon-α in children 1-6 years-old with HBeAg-positive chronic hepatitis B].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Article
- H3K9 acetylation-dependent CHAC1 transcription in dihydroartemisinin-induced hepatic stellate cell ferroptosis.Chinese medical journal · 2026Article
- The function and mechanism of protein acylation in the regulation of viral infection.Virulence · 2025Review
- Predictors of low-level viremia in chronic hepatitis B and the efficacy of pegylated interferon-alpha: a real-world study.Virology journal · 2025Article
- [HDAC2-mediated H3K27 acetylation promotes the proliferation and migration of hepatocellular carcinoma cells].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- Novel histone modifications and liver cancer: emerging frontiers in epigenetic regulation.Clinical epigenetics · 2025Review
- Advance in molecular mechanisms underlying diabetes related to viral hepatitis infection.Frontiers in cellular and infection microbiology · 2025Review
- Epigenetic regulation and its therapeutic potential in hepatitis B virus covalently closed circular DNA.Genes & diseases · 2025Review
- p-STAT3-elevated E3 ubiquitin ligase DTX4 confers the stability of HBV cccDNA by ubiquitinating APOBEC3B in liver.Theranostics · 2024Article
- METTL14 Induced NJournal of Cancer · 2024Article
- The role of HBV cccDNA in occult hepatitis B virus infection.Molecular and cellular biochemistry · 2023Review
- Oncometabolites drive tumorigenesis by enhancing protein acylation: from chromosomal remodelling to nonhistone modification.Journal of experimental & clinical cancer research : CR · 2022Review
- Role of epigenetic modification in interferon treatment of hepatitis B virus infection.Frontiers in immunology · 2022Review
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The epigenetic modification of hepatitis B virus (HBV) covalently closed circular DNA (cccDNA) plays a crucial role in cccDNA transcription and viral persistence. Interferon-α (IFN-α) is a pivotal agent against HBV cccDNA. However, the mechanism by which IFN-α modulates the epigenetic regulation of cccDNA remains poorly understood. In this study, we report that IFN-α2b enhances the histone deacetylase 3 (HDAC3)-mediated de-2-hydroxyisobutyrylation of histone H4 lysine 8 (H4K8) on HBV cccDNA minichromosome to restrict the cccDNA transcription in liver. By screening acetyltransferases and deacetylases, we identified that HDAC3 was an effective restrictor of HBV transcription and replication. Moreover, we found that HDAC3 was able to mediate the de-2-hydroxyisobutyrylation of H4K8 in HBV-expressing hepatoma cells. Then, the 2-hydroxyisobutyrylation of histone H4K8 (H4K8hib) was identified on the HBV cccDNA minichromosome, promoting the HBV transcription and replication. The H4K8hib was regulated by HDAC3 depending on its deacetylase domain in the system. The low level of HDAC3 and high level of H4K8hib were observed in the liver tissues from HBV-infected human liver-chimeric mice. The levels of H4K8hib on HBV cccDNA minichromosome were significantly elevated in the liver biopsy specimens from clinical hepatitis B patients, which was consistent with the high transcriptional activity of cccDNA. Strikingly, IFN-α2b effectively facilitated the histone H4K8 de-2-hydroxyisobutyrylation mediated by HDAC3 on the HBV cccDNA minichromosome in primary human hepatocytes and hepatoma cells, leading to the inhibition of HBV transcription and replication. Our finding provides new insights into the mechanism by which IFN-α modulates the epigenetic regulation of HBV cccDNA minichromosome.
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