Evidence map›Paper›PMID 41320130›Full record

ArticleTumour virus research2025

Hepatitis B viral DNA integration occurs within three days of infection and is enhanced by ATR inhibition.

Dong Li, Jochen M Wettengel, Harout Ajoyan, Vikki Ho, Gabriela Wu, Sarah Bae, Henrik Zhang, Delgerbat Boldbaatar, Jacob George, Mark W Douglas and 1 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Tumour virus research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed.

  1. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

Dong LiStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Jochen M WettengelInstitute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany; German Center for Infection Research (DZIF), Munich Partner Site, Munich, Germany.
Harout AjoyanStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Vikki HoStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Gabriela WuStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Sarah BaeStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Henrik ZhangStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Delgerbat BoldbaatarStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Jacob GeorgeStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia.
Mark W DouglasStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia; Sydney Infectious Diseases Institute, University of Sydney, Australia.
Thomas TuStorr Liver Centre, The Westmead Institute for Medical Research, Westmead Hospital and The University of Sydney, Westmead, NSW, Australia; Sydney Infectious Diseases Institute, University of Sydney, Australia. Electronic address: t.tu@sydney.edu.au.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Chronic hepatitis B virus (HBV) infection is a major risk factor for hepatocellular carcinoma, with viral DNA integration into the host genome playing a pivotal role in oncogenesis. While HBV integration has been historically considered an event occurring late in a chronic infection, sensitive assays have detected integrations early infection. This study investigates the specific timing and molecular mechanisms of HBV DNA integration using a replication deficient HBV reporter system (HBV-Zeo) in HepG2-NTCP cells. Infection of this virus followed by positive selection led to cellular colony formation, showing that the input virus is the substrate that undergoes integration. By inducing DNA double-strand breaks via X-ray irradiation at specific timepoints after HBV infection, we observed a 2-3-fold increase in integration frequency when cells are irradiated between 16 and 76 h post-infection. Pharmacological inhibition of DNA repair pathways in this specific time window revealed that suppression of homologous recombination (HR) via ATR inhibitors significantly enhances integration rates (2.4-2.8-fold), while microhomology-mediated end joining (MMEJ) inhibition reduced integration to 17 % of untreated controls. These findings suggest that MMEJ plays a key role in HBV DNA integration occurring within hours of HBV infection. Together, our results advance understanding of HBV-associated hepatocarcinogenesis and may inform therapeutic strategies to disrupt viral integration and mitigate HBV-associated liver cancer risk.

Indexed as

Ataxia Telangiectasia Mutated ProteinsDNA, ViralHepatitis B, ChronicHepatitis B virusVirus IntegrationDNA Breaks, Double-StrandedDNA End-Joining RepairDNA RepairHep G2 CellsHumansAtaxia Telangiectasia Mutated ProteinsATR protein, humanDNA, ViralDNA repair pathwaysDouble-stranded linear DNAHepatitis B virusHepatocellular carcinomaHomologous recombinationInsertional mutagenesisMicrohomology-mediated end joiningNon-homologous end joining

Identifiers

PMID41320130
PMCPMC12719184

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

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 Socratic graph.