ArticleJournal of virology2007
Characterization of the intracellular deproteinized relaxed circular DNA of hepatitis B virus: an intermediate of covalently closed circular DNA formation.
Article in Journal of virology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 229 papers, 1 of them a synthesis that pooled it.
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Who cites it
229 citing papers in PubMed, 1 synthesis or guideline pooled it, 327 citations in OpenAlex.
- Emerging Trends and Future Directions in the Development of Anti-hepatitis B Therapies: A Horizon Scanning Review.Clinical drug investigation · 2025Pooled it
- Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators.Virulence · 2026Article
- A novel highly specific qPCR assay for distinguishing HBV cccDNA from rcDNA following bisulfite pretreatment.Journal of virology · 2026Article
- The HBV basal core promoter mutation confers a replicative advantage and transcriptionally reprograms hepatocytes toward HCC subtypes.bioRxiv : the preprint server for biology · 2026Article
- Review
- Cell-based platforms for antiviral screening against hepatitis B virus: advantages, limitations, and future perspectives.Antiviral research · 2026Review
- Promotion of hepatitis B virus infection by extracellular apolipoprotein E.Journal of virology · 2026Article
- Generation of HBV cccDNA using single-stranded M13 phage DNA for authentic minichromosome functionality.Journal of virology · 2026Article
- Lead Optimization of Xanthone Derivatives as Hepatitis B Virus cccDNA Reducers: Design, Synthesis, and Bioevaluation.ACS medicinal chemistry letters · 2026Article
- Hepatitis B virus ribonuclease H inhibitors: Coming of age?Antiviral research · 2026Review
- 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
- 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
- Design, Synthesis, and Biological Evaluation of Highly Potent Boronic Acid (Boronate Ester)-Bearing Heteroaryldihydropyrimidine Derivatives as HBV Capsid Assembly Modulators.Journal of medicinal chemistry · 2025Article
- A hepatitis B virus RNA-sensing and RNA-editing-dependent reporter system.Journal of virology · 2025Article
- Hepatitis B Virus Nucleocapsid Assembly.Journal of molecular biology · 2025Review
- Discovery ofInternational journal of molecular sciences · 2025Article
- HBV p22-interacting protein C1QBP inhibits viral replication through impeding nucleocapsid formation and nuclear import.PLoS pathogens · 2025Article
- HBV capsid assembly modulators differentially modulate the assembly of wild-type and drug-resistant core protein chimeric nucleocapsids and empty capsids.PLoS pathogens · 2025Article
- Syndecan 2 proteoglycan serves as a hepatitis B virus cell attachment receptor.Journal of virology · 2025Article
- Host 3' flap endonuclease Mus81 plays a critical role in trimming the terminal redundancy of hepatitis B virus relaxed circular DNA during covalently closed circular DNA formation.PLoS pathogens · 2025Article
169 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 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Covalently closed circular DNA (cccDNA) of hepatitis B virus (HBV) is formed by conversion of capsid-associated relaxed circular DNA (rcDNA) via unknown mechanisms and exists in the nucleus of the infected hepatocyte as a minichromosome that serves as the transcription template for viral RNAs. To study the molecular pathway of cccDNA formation and its regulation by viral and cellular factors, we have established a cell line that supports the replication of an envelope protein-deficient HBV genome in a tetracycline-inducible manner. Following induction of HBV replication, the cells accumulate higher levels of cccDNA as well as larger amounts of deproteinized rcDNA (DP-rcDNA) than cells that replicate wild-type HBV genomes. These results indicate that HBV envelope proteins negatively regulate cccDNA formation, and conversion of DP-rcDNA into cccDNA is a rate-limiting step of cccDNA formation in HepG2 cells. Detailed analyses reveal the following: (i) DP-rcDNA exists in both cytoplasm and nucleus; (ii) while nuclear DP-rcDNA is sensitive to DNase I digestion, a small fraction of cytoplasmic DP-rcDNA is DNase I resistant; (iii) both DNase I-sensitive and -resistant cytoplasmic DP-rcDNAs cosediment with capsids and can be immunoprecipitated with HBV core antibody; and (iv) a primer extension assay maps the 5' end of the minus strand of DP-rcDNA at the authentic end of virion rcDNA. Hence, our results favor a hypothesis that the removal of viral polymerase protein covalently linked to the 5' end of the minus-strand DNA occurs inside the capsid in the cytoplasm and most possibly via a reaction that cleaves the phosphodiester bond between the tyrosine of the polymerase and the 5' phosphoryl group of minus-strand DNA.
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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.