ArticleJournal of hepatology2018
Hepatitis B virus genome recycling and de novo secondary infection events maintain stable cccDNA levels.
Article in Journal of hepatology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05965388 (Predictive Value of HBV pgRNA on Long-term Outcomes in Hepatitis B Patients Treated With Antiviral Therapy), which is not on this map. Cited by 142 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Predictive Value of HBV pgRNA on Long-term Outcomes in Hepatitis B Patients Treated With Antiviral Therapy
Who cites it
142 citing papers in PubMed, 1 synthesis or guideline pooled it, 223 citations in OpenAlex.
- KASL clinical practice guidelines for management of chronic hepatitis B.Clinical and molecular hepatology · 2022Guideline
- HBV serum RNA kinetics during nucleic acid polymers based therapy predict functional cure.Antiviral research · 2025Trial
- Single-Cell Hepatitis B Sequencing Reveals Distinct Viral Infection Events Consistent With Superinfection.The Journal of infectious diseases · 2026Article
- AAV-mediated delivery of CRISPR/Cas9 targeting conserved overlapping ORFs efficiently suppresses HBV replication in hepatocyte models.Biotechnology reports (Amsterdam, Netherlands) · 2026Article
- Therapeutic vaccination strategy targeting the PreS1 region of L-HBsAg for HBV/HDV co-infection.JHEP reports : innovation in hepatology · 2026Article
- Occult hepatitis B and risk of reactivation following switch to non-hepatitis B virus-active antiretroviral therapy in people with HIV.AIDS (London, England) · 2026Review
- Cell-based platforms for antiviral screening against hepatitis B virus: advantages, limitations, and future perspectives.Antiviral research · 2026Review
- A key role for the exoribonuclease XRN1 in regulating the hepatitis B viral transcriptome.iScience · 2026Article
- Review
- KASL clinical practice guidelines for management of chronic hepatitis B Endorsed by the East Asia Liver Alliance (EALA).Clinical and molecular hepatology · 2026Article
- Host mature tRNAome as a decoding switch regulates antiviral and proviral responses.Nature communications · 2026Article
- DNA and RNA editing for the therapy of human diseases: current status, challenges, and future prospects.Molecular biomedicine · 2026Review
- Chromatin remodeler BAF maintains HBV cccDNA transcriptional competence and represents a therapeutic target.Nucleic acids research · 2026Article
- Dynamics and Sensitivity of the Lifecycle of Hepatitis B Virus.Pathogens (Basel, Switzerland) · 2026Article
- Innate immune recognition and evasion strategies of hepatitis B virus: from DNA to RNA and viral proteins.Frontiers in immunology · 2026Review
- Targeting the innate immune system in treating hepatitis B: prospects for functional cure.Clinical and molecular hepatology · 2026Review
- Therapeutic hepatitis B vaccine employing DNA prime - MVA boost scheme requires additional priming with recombinant HBsAg to elicit an adequate antibody response.Frontiers in immunology · 2026Article
- Role of cccDNA in the Quest for HBV Cure- Implications for HIV-HBV Coinfection.Current HIV/AIDS reports · 2025Review
- Association of hepatitis B virus genomes with active chromatin hubs challenges host replication fidelity, leading to DNA damage.Journal of virology · 2025Article
- NTCP ubiquitination enables HBV infection.JHEP reports : innovation in hepatology · 2025Article
82 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
13 authors at 5 institutions in 3 countries.
Funding
Abstract
BACKGROUND &
aimsSeveral steps in the HBV life cycle remain obscure because of a lack of robust in vitro infection models. These steps include particle entry, formation and maintenance of covalently closed circular (ccc) DNA, kinetics of gene expression and viral transmission routes. This study aimed to investigate infection kinetics and cccDNA dynamics during long-term culture.
methodsWe selected a highly permissive HepG2-NTCP-K7 cell clone engineered to express sodium taurocholate co-transporting polypeptide (NTCP) that supports the full HBV life cycle. We characterized the replication kinetics and dynamics of HBV over six weeks of infection.
resultsHBV infection kinetics showed a slow infection process. Nuclear cccDNA was only detected 24 h post-infection and increased until 3 days post-infection (dpi). Viral RNAs increased from 3 dpi reaching a plateau at 6 dpi. HBV protein levels followed similar kinetics with HBx levels reaching a plateau first. cccDNA levels modestly increased throughout the 45-day study period with 5-12 copies per infected cell. Newly produced relaxed circular DNA within capsids was reimported into the nucleus and replenished the cccDNA pool. In addition to intracellular recycling of HBV genomes, secondary de novo infection events resulted in cccDNA formation. Inhibition of relaxed circular DNA formation by nucleoside analogue treatment of infected cells enabled us to measure cccDNA dynamics. HBV cccDNA decayed slowly with a half-life of about 40 days.
conclusionsAfter a slow infection process, HBV maintains a stable cccDNA pool by intracellular recycling of HBV genomes and via secondary infection. Our results provide important insights into the dynamics of HBV infection and support the future design and evaluation of new antiviral agents. LAY SUMMARY: Using a unique hepatocellular model system designed to support viral growth, we demonstrate that hepatitis B virus (HBV) has remarkably slow infection kinetics. Establishment of the episomal transcription template and the persistent form of the virus, so called covalently closed circular DNA, as well as viral transcription and protein expression all take a long time. Once established, HBV maintains a stable pool of covalently closed circular DNA via intracellular recycling of HBV genomes and through infection of naïve cells by newly formed virions.
Indexed as
Identifiers
What OpenQuestion holds
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.