ArticleProceedings of the National Academy of Sciences of the United States of America2009
Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 289 papers, 3 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
289 citing papers in PubMed, 3 syntheses or guidelines pooled it, 479 citations in OpenAlex.
- A Systematic Review of the Impact of Resveratrol on Viral Hepatitis and Chronic Viral Hepatitis-related Hepatocellular Carcinoma.Current molecular medicine · 2025Pooled it
- Hepatitis B infection and intrahepatic cholestasis of pregnancy: A systematic review and meta-analysis.Medicine · 2020Pooled it
- Applications of next-generation sequencing analysis for the detection of hepatocellular carcinoma-associated hepatitis B virus mutations.Journal of biomedical science · 2018Pooled it
- Natural products targeting hepatitis B virus X protein and HBx-associated pathways in HBV-related hepatocellular carcinoma: mechanisms and therapeutic potential.Pharmaceutical biology · 2026Review
- Metabolic Signatures for Liver Cancer Diagnosis and Mechanistic Insights: A Large-Scale, Multicenter Study.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Occult hepatitis B virus infection.Nature reviews. Gastroenterology & hepatology · 2026Review
- Chromatin Accessibility-Guided Targeting Identifies Structurally Constrained Regions in HBV cccDNA and Suppresses Viral Replication.International journal of molecular sciences · 2026Article
- A key role for the exoribonuclease XRN1 in regulating the hepatitis B viral transcriptome.iScience · 2026Article
- Review
- A Leap Forward in Vaccination - the Epigenetic Silencing of HIV by cVacc.Current HIV/AIDS reports · 2026Review
- ddOTs: A multiplexed quantitative ddPCR approach for resolving overlapping hepatitis B virus transcripts to decipher cccDNA-driven transcription.PLoS pathogens · 2026Article
- HBx-Associated Reactivation of the IGF2 Locus in Chronic HBV Infection and HBV-Related Hepatocarcinogenesis: Evidence Boundaries and Biomarker Implications.Biomedicines · 2026Review
- Generation of HBV cccDNA using single-stranded M13 phage DNA for authentic minichromosome functionality.Journal of virology · 2026Article
- Hepatitis B virus-induced hepatocellular carcinoma: HBx-associated epigenetic mechanisms and therapeutic opportunities.Cancer gene therapy · 2026Review
- Accuracy of Diagnostic Investigations in Monitoring Hepatitis B Virus Infection: Strengths, Limitations, and Emerging Biomarkers.International journal of molecular sciences · 2026Review
- The APOBEC3 family: a narrative review of an alternative therapeutic agent for hepatitis B virus-induced hepatocellular carcinoma.Journal of gastrointestinal oncology · 2026Review
- Insight into the Biology of Hepatitis B Virus and Recent Therapeutic Approaches.Current microbiology · 2026Review
- HBx interacts with the host YBX3 protein and up-regulates its expression to mediate efficient Hepatitis B viral replication.Frontiers in cellular and infection microbiology · 2026Article
- Role of cccDNA in the Quest for HBV Cure- Implications for HIV-HBV Coinfection.Current HIV/AIDS reports · 2025Review
- The SWI/SNF complex mediated chromatin remodeling promotes hepatitis B virus cccDNA transcription.Science China. Life sciences · 2025Article
229 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HBV cccDNA, the template for transcription of all viral mRNAs, accumulates in the nucleus of infected cells as a stable episome organized into minichromosomes by histones and non-histone viral and cellular proteins. Using a cccDNA-specific chromatin immunoprecipitation (ChIP)-based quantitative assay, we have previously shown that transcription of the HBV minichromosome is regulated by epigenetic changes of cccDNA-bound histones and that modulation of the acetylation status of cccDNA-bound H3/H4 histones impacts on HBV replication. We now show that the cellular histone acetyltransferases CBP, p300, and PCAF/GCN5, and the histone deacetylases HDAC1 and hSirt1 are all recruited in vivo onto the cccDNA. We also found that the HBx regulatory protein produced in HBV replicating cells is recruited onto the cccDNA minichromosome, and the kinetics of HBx recruitment on the cccDNA parallels the HBV replication. As expected, an HBV mutant that does not express HBx is impaired in its replication, and exogenously expressed HBx transcomplements the replication defects. p300 recruitment is severely impaired, and cccDNA-bound histones are rapidly hypoacetylated in cells replicating the HBx mutant, whereas the recruitment of the histone deacetylases hSirt1 and HDAC1 is increased and occurs at earlier times. Finally, HBx mutant cccDNA transcribes significantly less pgRNA. Altogether our results further support the existence of a complex network of epigenetic events that influence cccDNA function and HBV replication and identify an epigenetic mechanism (i.e., to prevent cccDNA deacetylation) by which HBx controls HBV replication.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.