ArticleProceedings of the National Academy of Sciences of the United States of America2004
Expansion and contraction of the hepatitis B virus transcriptional template in infected chimpanzees.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 106 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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Who cites it
106 citing papers in PubMed, 1 synthesis or guideline pooled it, 214 citations in OpenAlex.
- Association between the interferon-γ +874T/A polymorphism and susceptibility to hepatitis B virus infection: a meta-analysis.The Journal of international medical research · 2020Pooled it
- Rapid Turnover of Hepatitis B Virus Covalently Closed Circular DNA Indicated by Monitoring Emergence and Reversion of Signature-Mutation in Treated Chronic Hepatitis B Patients.Hepatology (Baltimore, Md.) · 2021Trial
- Mapping the Heterogeneity of Histone Modifications on Hepatitis B Virus DNA Using Liver Needle Biopsies Obtained from Chronically Infected Patients.Journal of virology · 2019Trial
- Trial
- Trial
- Hepatitis B virus covalently closed circular DNA formation in murine hepatic cells uncovers a late entry block.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Novel digital droplet inverse PCR assay shows that natural clearance of hepatitis B infection is associated with fewer viral integrations.Emerging microbes & infections · 2025Article
- Hepatitis B Virus Nucleocapsid Assembly.Journal of molecular biology · 2025Review
- Epigenetic regulation and its therapeutic potential in hepatitis B virus covalently closed circular DNA.Genes & diseases · 2025Review
- Tissue Determinants of Antiviral Immunity in the Liver.Zeitschrift fur Gastroenterologie · 2025Review
- mTOR Signaling: Roles in Hepatitis B Virus Infection and Hepatocellular Carcinoma.International journal of biological sciences · 2024Review
- Detection of Hepatitis B Virus Covalently Closed Circular DNA and Intermediates in Its Formation.Methods in molecular biology (Clifton, N.J.) · 2024Article
- IFN-γ: A Crucial Player in the Fight Against HBV Infection?Immune network · 2023Review
- Dynamics of Hepatitis B Virus Covalently Closed Circular DNA: A Mini-Review.Microorganisms · 2023Review
- Hepatitis B surface antigen reduction is associated with hepatitis B core-specific CD8Frontiers in immunology · 2023Article
- Review
- Constrained evolution of overlapping genes in viral host adaptation: Acquisition of glycosylation motifs in hepadnaviral precore/core genes.PLoS pathogens · 2022Article
- Review
- An age-structured model of hepatitis B viral infection highlights the potential of different therapeutic strategies.Scientific reports · 2022Article
- [A short half-life of cccDNA offer or ignite hope for hepatitis B cure under nucleos(t)ide analogues treatment].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Article
46 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
5 authors at 2 institutions in 1 country.
Funding
Abstract
We have previously shown that hepatitis B virus (HBV) replication is controlled by noncytolytic mechanisms that depend primarily on the effector functions of the CD8(+) T cell response, especially the production of IFN-gamma in the liver. The mechanisms that control the nuclear pool of viral covalently closed circular DNA (cccDNA) transcriptional template of HBV, which must be eliminated to eradicate infection, have been difficult to resolve. To examine those mechanisms, we quantitated intrahepatic HBV cccDNA levels in acutely infected chimpanzees whose virological, immunological, and pathological features were previously described. Our results demonstrate that the elimination kinetics of the cccDNA are more rapid than the elimination of HBV antigen-positive hepatocytes during the early phase of viral clearance, and they coincide with the influx of small numbers of IFN-gamma producing CD8(+) T cells into the liver. In contrast, terminal clearance of the cccDNA is associated with the peak of liver disease and hepatocellular turnover and with a surge of IFN-gamma producing CD8(+) T cells in the liver. Collectively, these results suggest that cccDNA clearance is a two-step process mediated by the cellular immune response. The first step reduces the pool of cccDNA molecules noncytolytically, probably by eliminating their relaxed circular DNA precursors and perhaps by destabilizing them. The second step enhances this process by destroying infected hepatocytes and triggering their turnover. Surprisingly, despite this multipronged response, traces of cccDNA persist indefinitely in the liver, likely providing a continuous antigenic stimulus that confers lifelong immunity.
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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.