Evidence map›Paper›PMID 35898957›Full record

ArticleJHEP reports : innovation in hepatology2022

Mitosis of hepatitis B virus-infected cells

Thomas Tu, Benno Zehnder, Jochen M Wettengel, Henrik Zhang, Sally Coulter, Vikki Ho, Mark W Douglas, Ulrike Protzer, Jacob George, Stephan Urban

Open access · goldAbstract read
In one paragraph

Article in JHEP reports : innovation in hepatology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.

0numbers the graph read from it
0cells of the map it votes in
20citing papers in PubMed
4.4field-weighted citation impact, top 5% of its field
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

20 citing papers in PubMed, 28 citations in OpenAlex.

  1. Review
  2. Article
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  4. Article
  5. Article
  6. Review
  7. Review
  8. Review
  9. Article
  10. Review
  11. HBV-Induced Carcinogenesis: Mechanisms, Correlation With Viral Suppression, and Implications for Treatment.Liver international : official journal of the International Association for the Study of the Liver · 2025
    Review
  12. Review
  13. Review
  14. Article
  15. Review
  16. Article
  17. Article
  18. [A conceptual framework for dynamics of cccDNA in hepatitis B virus].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2023
    Article
  19. Article
  20. 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

10 authors at 3 institutions in 2 countries.

Thomas TuStorr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Benno ZehnderDepartment of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany.
Jochen M WettengelInstitute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
Henrik ZhangStorr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Sally CoulterStorr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Vikki HoStorr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Mark W DouglasStorr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Ulrike ProtzerInstitute of Virology, Technische Universität München/Helmholtz Zentrum München, Munich, Germany.
Jacob GeorgeStorr Liver Centre, Westmead Clinical School and Westmead Institute for Medical Research, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia.
Stephan UrbanDepartment of Infectious Diseases, Molecular Virology, University Hospital Heidelberg, Heidelberg, Germany.
The University of Sydney · AUHeidelberg University · DEHelmholtz Zentrum München · DE

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Background & Aims: The chronicity of HBV (and resultant liver disease) is determined by intrahepatic persistence of the HBV covalently closed circular DNA (cccDNA), an episomal form that encodes all viral transcripts. Therefore, cccDNA is a key target for new treatments, with the ultimate therapeutic aim being its complete elimination. Although established cccDNA molecules are known to be stable in resting hepatocytes, we aimed to understand their fate in dividing cells using Methods: We infected HepG2-NTCP and HepaRG-NTCP cells with HBV and induced mitosis by passaging cells. We measured cccDNA copy number (by precise PCR assays) and HBV-expressing cells (by immunofluorescence) with wild-type HBV. We used reporter viruses expressing luciferase or RFP to track number of HBV-expressing cells over time after mitosis induction using luciferase assays and live imaging, respectively. Results: In all cases, we observed dramatic reductions in cccDNA levels, HBV-positive cell numbers, and cccDNA-dependent protein expression after each round of cell mitosis. The rates of reduction were highly consistent with mathematical models of a complete cccDNA loss in (as opposed to dilution into) daughter cells. Conclusions: Our results are concordant with previous animal models of HBV infection and show that HBV persistence can be efficiently overcome by inducing cell mitosis. These results support therapeutic approaches that induce liver turnover ( Lay summary: Chronic hepatitis B affects 300 million people (killing 884,000 per year) and is incurable. To cure it, we need to clear the HBV genome from the liver. In this study, we looked at how the virus behaves after a cell divides. We found that it completely clears the virus, making 2 new uninfected cells. Our work informs new approaches to develop cures for chronic hepatitis B infections.

Indexed as

cccDNA, covalently closed circular DNAcinqPCRcinqPCR, cccDNA inversion quantitative PCRCovalently closed circular DNAddPCR, digital droplet PCRdpi, days post-infectionGluc, Gaussia luciferaseHBc, HBV core proteinHepatitis B virusORF, open reading framerHBV, reporter HBVtRFP, turbo-RFPTTR, transthyretinViral persistenceWT, wild type

Identifiers

PMID35898957
PMCPMC9309680
OpenAlexW4282964067

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.