ArticleProceedings of the National Academy of Sciences of the United States of America2003
Single-cell analysis of covalently closed circular DNA copy numbers in a hepadnavirus-infected liver.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers.
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.
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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
66 citing papers in PubMed, 136 citations in OpenAlex.
- Cell-based platforms for antiviral screening against hepatitis B virus: advantages, limitations, and future perspectives.Antiviral research · 2026Review
- Replication-driven HBV cccDNA loss in chimeric mice with humanized livers.Journal of virology · 2025Article
- A single-cell digital PCR method tailored for quantification of HBV DNA positive cells in liver biopsy tissues.Journal of translational medicine · 2025Article
- Wnt/β-Catenin Signaling Regulates Hepatitis B Virus cccDNA Levels.International journal of molecular sciences · 2025Article
- Review
- Nonproductive Hepatitis B Virus Covalently Closed Circular DNA Generates HBx-Related Transcripts from the HBx/Enhancer I Region and Acquires Reactivation by Superinfection in Single Cells.Journal of virology · 2023Article
- Pathogenicity and virulence of Hepatitis B virus.Virulence · 2022Review
- Role of hepatitis B virus in development of hepatocellular carcinoma: Focus on covalently closed circular DNA.World journal of hepatology · 2022Review
- Approaches to quantifying hepatitis B virus covalently closed circular DNA.Clinical and molecular hepatology · 2022Review
- Review
- The Hepatitis B Virus Nucleocapsid-Dynamic Compartment for Infectious Virus Production and New Antiviral Target.Biomedicines · 2021Review
- Mechanism of Hepatitis B Virus cccDNA Formation.Viruses · 2021Review
- Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20.EMBO reports · 2021Article
- Early Steps of Hepatitis B Life Cycle: From Capsid Nuclear Import to cccDNA Formation.Viruses · 2021Review
- Early events in hepatitis B infection: the role of inoculum dose.Proceedings. Biological sciences · 2021Article
- Article
- Translational Strategies to Eliminate Chronic Hepatitis B in Children: Prophylaxis and Management in East Asian Countries.Frontiers in pediatrics · 2021Review
- The Hepatitis B Virus Interactome: A Comprehensive Overview.Frontiers in microbiology · 2021Review
- Estimating hepatitis B virus cccDNA persistence in chronic infection.Virus evolution · 2021Article
- Hepatitis B virus cccDNA: Formation, regulation and therapeutic potential.Antiviral research · 2020Review
6 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
6 authors at 2 institutions in 1 country.
Funding
Abstract
Hepatitis B virus (hepadnavirus) infections are maintained by the presence of a small and regulated number of episomal viral genomes [covalently closed circular DNA (cccDNA)] in the nuclei of infected cells. Although a number of studies have measured the mean copy number of cccDNA molecules in hepadnaviral-infected cells, the distribution of individual copy numbers have not been reported. Using a PCR-based assay, we examined the number of cccDNA molecules of the duck hepatitis B virus in single nuclei isolated from the liver of a chronically infected duck over the course of 131 days of infection. Nuclei were isolated from frozen serial biopsies and individually deposited into PCR microplates by flow sorting. Each nucleus was assayed by nested PCR for cccDNA and for cellular IFN-alpha genes as an internal control. We found that 90% of the nuclei assayed contained between 1 and 17 cccDNA molecules, with the remaining 10% containing more (90% confidence), and that differences in the mean number of copies and distribution of copy numbers occurred within the same animal at different times postinfection. Overall, the data suggest (i) that the number of cccDNA molecules per cell may fluctuate over time, and (ii) that, according to these fluctuations, a substantial fraction of cells may contain only one or a few copies. We infer from the results that infected hepatocytes express virus at different levels and that during cell division it is possible to segregate cells containing no cccDNA.
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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.