Evidence map›Paper›PMID 25092305›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2014

Modeling host interactions with hepatitis B virus using primary and induced pluripotent stem cell-derived hepatocellular systems.

Amir Shlomai, Robert E Schwartz, Vyas Ramanan, Ankit Bhatta, Ype P de Jong, Sangeeta N Bhatia, Charles M Rice

Open access · bronzeAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers.

0numbers the graph read from it
0cells of the map it votes in
159citing papers in PubMed
19.9field-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

159 citing papers in PubMed, 245 citations in OpenAlex.

  1. Article
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  10. In vitro liver models for toxicological research.Drug metabolism and pharmacokinetics · 2025
    Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Review
  16. Article
  17. Progress of Infection and Replication Systems of Hepatitis B Virus.ACS pharmacology & translational science · 2024
    Review
  18. Review
  19. Article
  20. Article

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

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

7 authors at 4 institutions in 2 countries.

Amir ShlomaiLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065;
Robert E SchwartzDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115;Department of Health Sciences and Technology.
Vyas RamananDepartment of Health Sciences and Technology.
Ankit BhattaLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065;
Ype P de JongLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065;Division of Gastroenterology and Hepatology, Department of Medicine, Center for the Study of Hepatitis C, Weill Cornell Medical College, New York, NY 10065; and.
Sangeeta N BhatiaDepartment of Medicine, Brigham and Women's Hospital, Boston, MA 02115;Department of Health Sciences and Technology,Department of Electrical Engineering and Computer Science,Broad Institute of MIT and Harvard, Cambridge, MA 02139Koch Institute for Integrative Cancer Research, andHoward Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, MA 02139; ricec@rockefeller.edu sbhatia@mit.edu.
Charles M RiceLaboratory of Virology and Infectious Disease, Center for the Study of Hepatitis C, The Rockefeller University, New York, NY 10065; ricec@rockefeller.edu sbhatia@mit.edu.
Rockefeller University · USBrigham and Women's Hospital · USDepartment of Medical Sciences · BYHoward Hughes Medical Institute · US

Funding

VIRUS PRODUCTION COREP30CA014051 · NCI · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · PI MATTHEW G. VANDER HEIDEN · 1985 to 2026
$93.9M
Transforming Translational Science and Education to Benefit Human HealthUL1TR000043 · NCATS · ROCKEFELLER UNIVERSITY · PI COLLER, BARRY · 2012 to 2015
$26.8M
Tissue Chips for Rare Disease: Adding Timothy Syndrome to the HeLIVaSkCa platformUH3EB017103 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2014 to 2016
$7.1M
Modeling human hepatotropic infections in complex tissue organoidsR01DK085713 · NIDDK · ROCKEFELLER UNIVERSITY · PI BHATIA, SANGEETA N., RICE, CHARLES M · 2009 to 2013
$5.6M
Integrated heart-liver-vascular systems for drug testing in human health and diseUH2EB017103 · NIBIB · COLUMBIA UNIV NEW YORK MORNINGSIDE · PI VUNJAK-NOVAKOVIC, GORDANA · 2012 to 2013
$1.7M
New Hepatocyte Model Systems to study Hepatitis B Virus InfectionK08DK101754 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI SCHWARTZ, ROBERT E · 2014 to 2018
$781k
The role of innate immune evasion in hepatitis C virus infectionK08DK090576 · NIDDK · WEILL MEDICAL COLL OF CORNELL UNIV · PI DE JONG, YPE PETER · 2011 to 2015
$760k
Howard Hughes Medical InstituteNCATS NIH HHS 8 UL1 TR000043NCATS NIH HHS UL1 TR000043NCI NIH HHS P30 CA014051NCI NIH HHS P30-CA14051NIBIB NIH HHS UH2 EB017103NIBIB NIH HHS UH3 EB017103NIDDK NIH HHS 1K08DK101754NIDDK NIH HHS DK085713NIDDK NIH HHS K08 DK090576NIDDK NIH HHS K08 DK101754NIDDK NIH HHS R01 DK085713
6 · The paper itself

Abstract

Hepatitis B virus (HBV) chronically infects 400 million people worldwide and is a leading driver of end-stage liver disease and liver cancer. Research into the biology and treatment of HBV requires an in vitro cell-culture system that supports the infection of human hepatocytes, and accurately recapitulates virus-host interactions. Here, we report that micropatterned cocultures of primary human hepatocytes with stromal cells (MPCCs) reliably support productive HBV infection, and infection can be enhanced by blocking elements of the hepatocyte innate immune response associated with the induction of IFN-stimulated genes. MPCCs maintain prolonged, productive infection and represent a facile platform for studying virus-host interactions and for developing antiviral interventions. Hepatocytes obtained from different human donors vary dramatically in their permissiveness to HBV infection, suggesting that factors--such as divergence in genetic susceptibility to infection--may influence infection in vitro. To establish a complementary, renewable system on an isogenic background in which candidate genetics can be interrogated, we show that inducible pluripotent stem cells differentiated into hepatocyte-like cells (iHeps) support HBV infection that can also be enhanced by blocking interferon-stimulated gene induction. Notably, the emergence of the capacity to support HBV transcriptional activity and initial permissiveness for infection are marked by distinct stages of iHep differentiation, suggesting that infection of iHeps can be used both to study HBV, and conversely to assess the degree of iHep differentiation. Our work demonstrates the utility of these infectious systems for studying HBV biology and the virus' interactions with host hepatocyte genetics and physiology.

Indexed as

Host-Pathogen InteractionsModels, BiologicalAntiviral AgentsCell DifferentiationHepatitis B virusHepatocytesHumansInduced Pluripotent Stem CellsAntiviral AgentsHBV persistenceinnate immunityviral hepatitis

Identifiers

PMID25092305
PMCPMC4143014
OpenAlexW2047743944

What OpenQuestion holds

Textmetadata
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.