Evidence map›Paper›PMID 27746336›Full record

ArticleJournal of hepatology2017

Human stem cell-derived hepatocytes as a model for hepatitis B virus infection, spreading and virus-host interactions.

Yuchen Xia, Arnaud Carpentier, Xiaoming Cheng, Peter Daniel Block, Yao Zhao, Zhensheng Zhang, Ulrike Protzer, T Jake Liang

Abstract read
In one paragraph

Article in Journal of hepatology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.

0numbers the graph read from it
0cells of the map it votes in
89citing papers in PubMed
10.7field-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

89 citing papers in PubMed, 137 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Review
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  6. Review
  7. Article
  8. Article
  9. Article
  10. Hepatitis B and D virus entry.Nature reviews. Microbiology · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Review
  15. Progress of Infection and Replication Systems of Hepatitis B Virus.ACS pharmacology & translational science · 2024
    Review
  16. Article
  17. Review
  18. Article
  19. Stem Cell-Derived Hepatocyte-Like Cells for Hepatitis B Virus Infection.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  20. Nucleolin binds to and regulates transcription of hepatitis B virus covalently closed circular DNA minichromosome.Proceedings of the National Academy of Sciences of the United States of America · 2023
    Article

29 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 2 countries.

Yuchen XiaLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Arnaud CarpentierLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Xiaoming ChengLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Peter Daniel BlockLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Yao ZhaoLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Zhensheng ZhangLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States.
Ulrike ProtzerInstitute of Virology, Technical University of Munich/Helmholtz Zentrum München, 81675 Munich, Germany; German Center for Infection research (DZIF), Munich partner site, Germany.
T Jake LiangLiver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United States. Electronic address: jakel@bdg10.niddk.nih.gov.
National Institute of Diabetes and Digestive and Kidney Diseases · USHelmholtz Zentrum München · DENational Institutes of Health · US

Funding

Molecular Mechanisms Of Hepatitis B Viral Pathogenesis And PersistenceZIADK054500 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 2009 to 2025
$20.3M
Therapy, Vaccine and Model Development in Viral Hepatitis and Liver DiseasesZIADK054505 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 2009 to 2025
$17.5M
MOLECULAR MECHANISMS OF HEPATITIS B VIRAL PATHOGENESIS AND PERSISTENCEZ01DK054500 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 1997 to 2008
$927k
Clinical Significance&Molecular Pathology Of Hepatitis BZ01DK054501 · NIDDK · NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES · PI LIANG, T. JAKE · 1997 to 2008
$927k
Intramural NIH HHS Z01 DK054500Intramural NIH HHS Z01 DK054501
6 · The paper itself

Abstract

BACKGROUND &

aimsOne major obstacle of hepatitis B virus (HBV) research is the lack of efficient cell culture system permissive for viral infection and replication. The aim of our study was to establish a robust HBV infection model by using hepatocyte-like cells (HLCs) derived from human pluripotent stem cells.

methodsHLCs were differentiated from human embryonic stem cells and induced pluripotent stem cells. Maturation of hepatocyte functions was determined. After HBV infection, total viral DNA, cccDNA, total viral RNA, pgRNA, HBeAg and HBsAg were measured.

resultsMore than 90% of the HLCs expressed strong signals of human hepatocyte markers, like albumin, as well as known host factors required for HBV infection, suggesting that these cells possessed key features of mature hepatocytes. Notably, HLCs expressed the viral receptor sodium-taurocholate cotransporting polypeptide more stably than primary human hepatocytes (PHHs). HLCs supported robust infection and some spreading of HBV. Finally, by using this model, we identified two host-targeting agents, genistin and PA452, as novel antivirals.

conclusionsStem cell-derived HLCs fully support HBV infection. This novel HLC HBV infection model offers a unique opportunity to advance our understanding of the molecular details of the HBV life cycle; to further characterize virus-host interactions and to define new targets for HBV curative treatment. LAY SUMMARY: Our study used human pluripotent stem cells to develop hepatocyte-like cells (HLCs) capable of expressing hepatocyte markers and host factors important for HBV infection. These cells fully support HBV infection and virus-host interactions, allowing for the identification of two novel antiviral agents. Thus, stem cell-derived HLCs provide a highly physiologically relevant system to advance our understanding of viral life cycle and provide a new tool for antiviral drug screening and development.

Indexed as

Antiviral AgentsCell DifferentiationCell LineCells, CulturedDrug DiscoveryEmbryonic Stem CellsHepatitis BHepatitis B virusHepatocytesHost-Pathogen InteractionsHumansInduced Pluripotent Stem CellsModels, BiologicalStem CellsVirus ReplicationAntiviral AgentsAntiviral agentsAntiviralsDNAHepatitis B virusHepatocytesModelStem cellViral

Identifiers

PMID27746336
PMCPMC5316493
OpenAlexW2535870561

What OpenQuestion holds

Textmetadata
LicenceTDM
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.