ArticleProceedings of the National Academy of Sciences of the United States of America2005
Clonal expansion of hepatocytes during chronic woodchuck hepatitis virus infection.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 106 citations in OpenAlex.
- 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
- Hepatitis B viral DNA integration occurs within three days of infection and is enhanced by ATR inhibition.Tumour virus research · 2025Article
- Novel digital droplet inverse PCR assay shows that natural clearance of hepatitis B infection is associated with fewer viral integrations.Emerging microbes & infections · 2025Article
- Development of a long-read high-throughput chromatin conformation capture method for evaluating bothbioRxiv : the preprint server for biology · 2025Article
- Review
- Two fragments of HBV DNA integrated into chrX: 11009033 and its genetic regulation in HepG2.2.15.Molecular medicine reports · 2023Article
- Biographical Feature: William (Bill) S. Mason.Journal of virology · 2023Article
- Mitosis of hepatitis B virus-infected cellsJHEP reports : innovation in hepatology · 2022Article
- In situ analysis of hepatitis B virus (HBV) antigen and DNA in HBV-induced hepatocellular carcinoma.Diagnostic pathology · 2022Article
- Hepatitis B Virus DNA Integration, Chronic Infections and Hepatocellular Carcinoma.Microorganisms · 2021Review
- HBV Integration Induces Complex Interactions between Host and Viral Genomic Functions at the Insertion Site.Journal of clinical and translational hepatology · 2021Review
- Application of the woodchuck animal model for the treatment of hepatitis B virus-induced liver cancer.World journal of gastrointestinal oncology · 2021Review
- Hepatitis B Virus DNA Integration and Clonal Expansion of Hepatocytes in the Chronically Infected Liver.Viruses · 2021Review
- Persistence of Hepatitis B Virus Infection: A Multi-Faceted Player for Hepatocarcinogenesis.Frontiers in microbiology · 2021Review
- Translational Strategies to Eliminate Chronic Hepatitis B in Children: Prophylaxis and Management in East Asian Countries.Frontiers in pediatrics · 2021Review
- A Translational Hepatic Artery Infusion (HAI) Model for Hepatocellular Carcinoma in Woodchucks.The Journal of surgical research · 2020Article
- Integration of hepatitis B virus DNA into p21-activated kinase 3 (PAK3) gene in HepG2.2.15 cells.Virus genes · 2020Article
- Sequence analysis of integrated hepatitis B virus DNA during HBeAg-seroconversion.Emerging microbes & infections · 2018Article
- Review
- Ideal Cure for Hepatitis B Infection: The Target is in Sight.Journal of clinical and experimental hepatology · 2018Review
Corrections and comments
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic hepadnavirus infections cause liver damage with ongoing death and regeneration of hepatocytes. In the present study we set out to quantify the extent of liver turnover by measuring the clonal proliferation of hepatocytes by using integrated viral DNA as a genetic marker for individual hepatocyte lineages. Liver tissue from woodchucks with chronic woodchuck hepatitis virus (WHV) infection was assayed for randomly integrated viral DNA by using inverse PCR. Serial endpoint dilution of viral-cell junction fragments into 96-well plates, followed by nested PCR and DNA sequencing, was used to determine the copy number of specific viral cell junctions as a measure of the clonal distribution of infected cell subpopulations. The results indicated that the livers contained a minimum of 100,000 clones of >1,000 cells containing integrated DNA, representing at least 0.2% of the hepatocyte population of the liver. Because cells with integrated WHV DNA comprised only 1-2% of total liver cells, it is likely that the total number of clones far exceeds this estimate, with as much as one-half of the liver derived from high copy clones of >1,000 cells. It may be inferred that these clones have a strong selective growth or survival advantage. The results provide evidence for a large amount of hepatocyte proliferation and selection having occurred during the period of chronic WHV infection ( approximately 1.5 years) in these animals.
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