Evidence map›Paper›PMID 33969602›Full record

ArticleEMBO reports2021

Interferon-induced degradation of the persistent hepatitis B virus cccDNA form depends on ISG20.

Daniela Stadler, Martin Kächele, Alisha N Jones, Julia Hess, Christian Urban, Jessica Schneider, Yuchen Xia, Andreas Oswald, Firat Nebioglu, Romina Bester and 15 more

Open access · bronzeAbstract read
In one paragraph

Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.

0numbers the graph read from it
0cells of the map it votes in
46citing papers in PubMed
8.6field-weighted citation impact, top 1% 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

46 citing papers in PubMed, 72 citations in OpenAlex.

  1. Trial
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. ISG20 RestrictsMicroorganisms · 2025
    Article
  11. Review
  12. Current status of drug therapy for chronic hepatitis B.World journal of gastroenterology · 2025
    Article
  13. Review
  14. Article
  15. Review
  16. Article
  17. Hepatitis B cure: Current situation and prospects.World journal of hepatology · 2024
    Review
  18. Review
  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

25 authors at 5 institutions in 2 countries.

Daniela StadlerInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.ORCID 0000-0002-7342-9751
Martin KächeleInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Alisha N JonesInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Julia HessResearch Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany.
Christian UrbanInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.ORCID 0000-0002-4080-2468
Jessica SchneiderInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Yuchen XiaInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Andreas OswaldInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Firat NebiogluDepartment of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany.
Romina BesterInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Felix LasitschkaInstitute of Pathology (DZIF tissue bank), University of Heidelberg, Heidelberg, Germany.
Marc RingelhanInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.ORCID 0000-0003-3131-5657
Chunkyu KoInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Wen-Min ChouInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Arie GeerlofInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Maarten A van de KlundertInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Jochen M WettengelInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Peter SchirmacherInstitute of Pathology (DZIF tissue bank), University of Heidelberg, Heidelberg, Germany.
Mathias HeikenwälderGerman Center for Infection Research (DZIF), Heidelberg, Germany.
Sabrina SchreinerInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.
Ralf BartenschlagerDepartment of Infectious Diseases, Molecular Virology, University of Heidelberg, Heidelberg, Germany.ORCID 0000-0001-5601-9307
Andreas PichlmairInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.ORCID 0000-0002-0166-1367
Michael SattlerInstitute of Structural Biology, Helmholtz Zentrum München, Neuherberg, Germany.
Kristian UngerResearch Unit Radiation Cytogenetics, Helmholtz Zentrum München, Neuherberg, Germany.
Ulrike ProtzerInstitute of Virology, School of Medicine, Technical University of Munich / Helmholtz Zentrum München, Munich, Germany.ORCID 0000-0002-9421-1911
Helmholtz Zentrum München · DECenter for Integrated Protein Science Munich · DEHeidelberg University · DEGerman Cancer Research Center · DETUM Klinikum · DE

Funding

ALIOS BioPharmaDeutsche Forschungsgemeinschaft (DFG) 272983813-TRR179Deutsche Forschungsgemeinschaft (DFG) TRR237
6 · The paper itself

Abstract

Hepatitis B virus (HBV) persists by depositing a covalently closed circular DNA (cccDNA) in the nucleus of infected cells that cannot be targeted by available antivirals. Interferons can diminish HBV cccDNA via APOBEC3-mediated deamination. Here, we show that overexpression of APOBEC3A alone is not sufficient to reduce HBV cccDNA that requires additional treatment of cells with interferon indicating involvement of an interferon-stimulated gene (ISG) in cccDNA degradation. Transcriptome analyses identify ISG20 as the only type I and II interferon-induced, nuclear protein with annotated nuclease activity. ISG20 localizes to nucleoli of interferon-stimulated hepatocytes and is enriched on deoxyuridine-containing single-stranded DNA that mimics transcriptionally active, APOBEC3A-deaminated HBV DNA. ISG20 expression is detected in human livers in acute, self-limiting but not in chronic hepatitis B. ISG20 depletion mitigates the interferon-induced loss of cccDNA, and co-expression with APOBEC3A is sufficient to diminish cccDNA. In conclusion, non-cytolytic HBV cccDNA decline requires the concerted action of a deaminase and a nuclease. Our findings highlight that ISGs may cooperate in their antiviral activity that may be explored for therapeutic targeting.

Indexed as

DNA, CircularHepatitis B virusAntiviral AgentsCytidine DeaminaseDNA, ViralExoribonucleasesHumansInterferonsProteinsVirus ReplicationAntiviral AgentsAPOBEC3A protein, humanCytidine DeaminaseDNA, CircularDNA, ViralExoribonucleasesInterferonsISG20 protein, humanProteinsAPOBEC3Achronic hepatitis BHBVinterferon alphainterferon gamma

Identifiers

PMID33969602
PMCPMC8183418
OpenAlexW3161331162

What Socratic 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 Socratic graph.