ArticleAntiviral research2016
Establishment of an inducible HBV stable cell line that expresses cccDNA-dependent epitope-tagged HBeAg for screening of cccDNA modulators.
Article in Antiviral research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 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.
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
47 citing papers in PubMed, 61 citations in OpenAlex.
- Dual HBV cccDNA-linked HiBiT reporter hepatocyte models for screening of candidate cccDNA modulators.Virulence · 2026Article
- Review
- Cell-based platforms for antiviral screening against hepatitis B virus: advantages, limitations, and future perspectives.Antiviral research · 2026Review
- Identification of glycogen synthase kinase 3alpha/beta as a host factor required for HBV transcription using high-throughput screening.Hepatology (Baltimore, Md.) · 2025Article
- Mechanisms underlying delayed loss of HBeAg and HBV DNA following HBsAg seroclearance in PEG-IFNα treated patients of chronic hepatitis B.Emerging microbes & infections · 2025Article
- HBV p22-interacting protein C1QBP inhibits viral replication through impeding nucleocapsid formation and nuclear import.PLoS pathogens · 2025Article
- Epigenetic drugs against human DNA viruses and retroviruses.Antiviral research · 2025Review
- The Evolution of Cell Culture Systems to Study Hepatitis B Virus Pathogenesis and Antiviral Susceptibility.Viruses · 2025Review
- Function of Interferon Lambda Receptor 1 Variants in Stem Cell-Derived Hepatocytes with Abrogated EndogenousJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 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
- Exploring the tolerable region for HiBiT tag insertion in the hepatitis B virus genome.mSphere · 2024Article
- NEDD4 family ubiquitin ligase AIP4 interacts with Alix to enable HBV naked capsid egress in an Alix ubiquitination-independent manner.PLoS pathogens · 2024Article
- Interferon lambda receptor-1 isoforms differentially influence gene expression and HBV replication in stem cell-derived hepatocytes.Antiviral research · 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
- cccDNA-Targeted Drug Screen Reveals a Class of Antihistamines as Suppressors of HBV Genome Levels.Biomolecules · 2023Article
- Synthetic gRNA/Cas9 ribonucleoprotein targeting HBV DNA inhibits viral replication.Journal of medical virology · 2023Article
- Screening of an epigenetic compound library identifies BRD4 as a potential antiviral target for hepatitis B virus covalently closed circular DNA transcription.Antiviral research · 2023Article
- The hepatitis B virus pre-core protein p22 suppresses TNFα-induced apoptosis by regulating the NF-κB pathway.American journal of translational research · 2023Article
- Article
- Hepatitis B virus X protein counteracts high mobility group box 1 protein-mediated epigenetic silencing of covalently closed circular DNA.PLoS pathogens · 2022Article
Corrections and comments
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Authors and funding
8 authors at 6 institutions in 1 country.
Funding
Abstract
Hepatitis B virus (HBV) covalently closed circular (ccc) DNA is essential to the virus life cycle, its elimination during chronic infection is considered critical to a durable therapy but has not been achieved by current antivirals. Despite being essential, cccDNA has not been the major target of high throughput screening (HTS), largely because of the limitations of current HBV tissue culture systems, including the impracticality of detecting cccDNA itself. In response to this need, we have previously developed a proof-of-concept HepDE19 cell line in which the production of wildtype e antigen (HBeAg) is dependent upon cccDNA. However, the existing assay system is not ideal for HTS because the HBeAg ELISA cross reacts with a viral HBeAg homologue, which is the core antigen (HBcAg) expressed largely in a cccDNA-independent fashion in HepDE19 cells. To further improve the assay specificity, we report herein a "second-generation" cccDNA reporter cell line, termed HepBHAe82. In the similar principle of HepDE19 line, an in-frame HA epitope tag was introduced into the precore domain of HBeAg open reading frame in the transgene of HepBHAe82 cells without disrupting any cis-element critical for HBV replication and HBeAg secretion. A chemiluminescence ELISA assay (CLIA) for the detection of HA-tagged HBeAg with HA antibody serving as capture antibody and HBeAb serving as detection antibody has been developed to eliminate the confounding signal from HBcAg. The miniaturized HepBHAe82 cell based assay system exhibits high level of cccDNA-dependent HA-HBeAg production and high specific readout signals with low background. We have also established a HepHA-HBe4 cell line expressing transgene-dependent HA-HBeAg as a counter screen to identify HBeAg inhibitors. The HepBHAe82 system is amenable to antiviral HTS development, and can be used to identify host factors that regulate cccDNA metabolism and transcription.
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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.