Evidence map›Paper›PMID 36591611›Full record

ArticleGut2022

Cell-based cccDNA reporter assay combined with functional genomics identifies YBX1 as HBV cccDNA host factor and antiviral candidate target.

Eloi R Verrier, Gaëtan Ligat, Laura Heydmann, Katharina Doernbrack, Julija Miller, Anne Maglott-Roth, Frank Jühling, Houssein El Saghire, Margaux J Heuschkel, Naoto Fujiwara and 11 more

Open access · hybridAbstract read
In one paragraph

Article in Gut, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
2.2field-weighted citation impact, top 12% 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

13 citing papers in PubMed, 16 citations in OpenAlex.

  1. Article
  2. Review
  3. EIF4H and YBX1 are essential host factors for hepatitis E virus replication and pathogenesis.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Review
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
  11. CAM-A-dependent HBV core aggregation induces apoptosis through ANXA1.JHEP reports : innovation in hepatology · 2024
    Article
  12. Article
  13. Review
4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

21 authors at 7 institutions in 4 countries.

Eloi R VerrierUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France Thomas.Baumert@unistra.fr e.verrier@unistra.fr michael.nassal@uniklinik-freiburg.de.
Gaëtan LigatUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.ORCID http://orcid.org/0000-0003-1237-1936
Laura HeydmannUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.
Katharina DoernbrackDepartment of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Freiburg, Germany.
Julija MillerDepartment of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Freiburg, Germany.
Anne Maglott-RothIGBMC, Plateforme de Criblage Haut-débit, Illkirch, France.
Frank JühlingUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.
Houssein El SaghireUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.
Margaux J HeuschkelUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.
Naoto FujiwaraDepartment of Internal Medicine, Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.ORCID http://orcid.org/0000-0002-4109-3421
Sen-Yung HsiehDepartment of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
Yujin HoshidaDepartment of Internal Medicine, Liver Tumor Translational Research Program, Simmons Comprehensive Cancer Center, Division of Digestive and Liver Diseases, University of Texas Southwestern Medical Center, Dallas, Texas, USA.
David E RootBroad Institute of Massachusetts Institute of Technology and Harvard, Cambridge, Massachusetts, USA.
Emanuele FelliUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.
Patrick PessauxUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.
Atish MukherjiUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.
Laurent MaillyUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.
Catherine SchusterUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France.ORCID http://orcid.org/0000-0001-7281-4511
Laurent BrinoIGBMC, Plateforme de Criblage Haut-débit, Illkirch, France.
Michael NassalDepartment of Internal Medicine II/Molecular Biology, University Hospital Freiburg, Freiburg, Germany Thomas.Baumert@unistra.fr e.verrier@unistra.fr michael.nassal@uniklinik-freiburg.de.ORCID http://orcid.org/0000-0003-2204-9158
Thomas F BaumertUniversité de Strasbourg, Inserm, Institut de Recherche sur les Maladies Virales et Hépatiques UMRS 1110, Strasbourg, France Thomas.Baumert@unistra.fr e.verrier@unistra.fr michael.nassal@uniklinik-freiburg.de.ORCID http://orcid.org/0000-0002-8864-2168
Inserm · FRInstitut de génétique et de biologie moléculaire et cellulaire · FRThe University of Texas Southwestern Medical Center · USUniversity Medical Center Freiburg · DEBroad Institute · USChang Gung Memorial Hospital · TWUniversity of Freiburg · DE

Funding

Trial of Statins for Chemoprevention in Hepatocellular CarcinomaR01CA255621 · NCI · MASSACHUSETTS GENERAL HOSPITAL · PI CHUNG, RAYMOND T, HOSHIDA, YUJIN · 2021 to 2025
$3.6M
Reverse-engineering precision liver cancer chemopreventionR01CA233794 · NCI · UT SOUTHWESTERN MEDICAL CENTER · PI HOSHIDA, YUJIN · 2019 to 2023
$3.5M
NCI NIH HHS R01 CA233794NCI NIH HHS R01 CA255621
6 · The paper itself

Abstract

objectivesChronic hepatitis B virus (HBV) infection is a leading cause of liver disease and hepatocellular carcinoma. A key feature of HBV replication is the synthesis of the covalently close circular (ccc)DNA, not targeted by current treatments and whose elimination would be crucial for viral cure. To date, little is known about cccDNA formation. One major challenge to address this urgent question is the absence of robust models for the study of cccDNA biology.

designWe established a cell-based HBV cccDNA reporter assay and performed a loss-of-function screen targeting 239 genes encoding the human DNA damage response machinery.

resultsOvercoming the limitations of current models, the reporter assay enables to quantity cccDNA levels using a robust ELISA as a readout. A loss-of-function screen identified 27 candidate cccDNA host factors, including Y box binding protein 1 (YBX1), a DNA binding protein regulating transcription and translation. Validation studies in authentic infection models revealed a robust decrease in HBV cccDNA levels following silencing, providing proof-of-concept for the importance of YBX1 in the early steps of the HBV life cycle. In patients,

conclusionOur cell-based reporter assay enables the discovery of HBV cccDNA host factors including YBX1 and is suitable for the characterisation of cccDNA-related host factors, antiviral targets and compounds.

Indexed as

antiviral therapyhepatitis B

Identifiers

PMID36591611
PMCPMC10423543
OpenAlexW4312030273

What OpenQuestion 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 OpenQuestion graph.