ArticleJournal of hepatology2017
HBVcircle: A novel tool to investigate hepatitis B virus covalently closed circular DNA.
Article in Journal of hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.
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Who cites it
44 citing papers in PubMed, 80 citations in OpenAlex.
- Cell-based platforms for antiviral screening against hepatitis B virus: advantages, limitations, and future perspectives.Antiviral research · 2026Review
- Generation of HBV cccDNA using single-stranded M13 phage DNA for authentic minichromosome functionality.Journal of virology · 2026Article
- [Advances in the construction and application of a novel liver organoid model for hepatitis B virus infection].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Adenine Base Editing Potently Suppresses Hepatitis B Surface Antigen Expression and Inhibits Hepatitis D Virus Release.bioRxiv : the preprint server for biology · 2026Article
- Progress and prospect of minicircle as a minimized non-viral DNA vector in gene therapy and regenerative medicine.Molecular therapy. Nucleic acids · 2025Review
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- Aglycone Polyether Ionophores Affecting Actin Filaments as Broad-Spectrum Antiviral Agents.ACS pharmacology & translational science · 2025Article
- Host factor RBM25 promotes HBV replication through Yin Yang 1-mediated cccDNA transcription.Virologica Sinica · 2025Article
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- Development of a dual channel detection system for pan-genotypic simultaneous quantification of hepatitis B and delta viruses.Emerging microbes & infections · 2024Article
- SARS-CoV-2 nsp13 suppresses hepatitis B virus replication by targeting cccDNA transcription.Journal of virology · 2024Article
- Applications of CRISPR/Cas as a Toolbox for Hepatitis B Virus Detection and Therapeutics.Viruses · 2024Review
- Progress of Infection and Replication Systems of Hepatitis B Virus.ACS pharmacology & translational science · 2024Review
- A nucleosome switch primes Hepatitis B Virus infection.bioRxiv : the preprint server for biology · 2024Article
- G-quadruplexes control hepatitis B virus replication by promoting cccDNA transcription and phase separation in hepatocytes.Nucleic acids research · 2024Article
- Cytosine base editing inhibits hepatitis B virus replication and reduces HBsAg expressionMolecular therapy. Nucleic acids · 2024Article
- Nucleolin binds to and regulates transcription of hepatitis B virus covalently closed circular DNA minichromosome.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
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- Development and characterization of a chronic hepatitis B murine model with a mutation in the START codon of an HBV polymerase.Physiological research · 2023Article
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND &
aimsHepatitis B virus (HBV) covalently closed circular DNA (cccDNA) persists as a stable episome in infected hepatocytes and serves as a template for the transcription of all viral genes. Due to the narrow host range of HBV, the development of a robust mouse model that supports cccDNA-dependent viral replication is a key hurdle in the development of novel HBV therapeutics. This study aimed to develop a novel tool to investigate HBV cccDNA.
methodsThrough minicircle technology, HBVcircle, a recombinant cccDNA, was easily generated and extracted from a genetically engineered E. coli strain. We characterized the performance of HBVcircle in cell culture by transfection and in immunocompetent mice by hydrodynamic injection (HDI).
resultsWe demonstrated that HBVcircle formed authentic cccDNA-like molecules in vitro in transiently transfected hepatic cells and in vivo in mouse liver after HDI. HBVcircle supported high levels and persistent HBV replication. In addition, we investigated different factors affecting HBV in vivo replication and persistence, including the host genetic background, vector design and dosage, viral genes and genotypes, and immune activation status. Furthermore, different classes of anti-HBV drugs were also assessed with the HBVcircle system.
conclusionCompared with previous reported HBV mouse models which employ other viral vectors to introduce overlength HBV genomes, viral gene expression and associated phenotypes are entirely driven by cccDNA-like viral genomes in the HBVcircle mouse model. Therefore, the HBVcircle is a close mimic of cccDNA, and it represents a novel tool for addressing HBV cccDNA related biological questions and for anti-HBV drug discovery. LAY SUMMARY: To establish a mouse model that supports cccDNA-dependent transcription, a novel tool named HBVcircle, was developed with minicircle technology. HBVcircle formed authentic cccDNA-like molecules in hepatocytes, and supported high levels and persistent HBV replication in vivo. The HBVcircle is a close mimic of cccDNA, and it represents a novel tool for addressing HBV cccDNA related biological questions and for anti-HBV drug discovery.
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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.