ArticlePLoS pathogens2012
Productive hepatitis C virus infection of stem cell-derived hepatocytes reveals a critical transition to viral permissiveness during differentiation.
Article in PLoS pathogens, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers, 1 of them a synthesis that pooled it.
What it found
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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.
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.
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Who cites it
88 citing papers in PubMed, 1 synthesis or guideline pooled it, 170 citations in OpenAlex.
- Pooled it
- Application of Induced Pluripotent Stem Cells (iPSCs) in Hereditary and Viral Diseases of the Liver: Modeling and Treatment.International journal of molecular sciences · 2025Review
- Article
- Single-cell analysis of mature hepatocytes reveals an IRF1-driven restriction of HDV infection.JHEP reports : innovation in hepatology · 2025Article
- IFITM1/OVOL1 Axis Is a Novel Regulator of the Expansion of the Limbal Epithelial Stem/Early Transient Amplifying Cell Population.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2025Article
- An hepatitis B and D virus infection model using human pluripotent stem cell-derived hepatocytes.EMBO reports · 2024Article
- Immortalized hepatocyte-like cells: A competent hepatocyte model for studying clinical HCV isolate infection.PloS one · 2024Article
- Intrinsic antiviral immunity of barrier cells revealed by an iPSC-derived blood-brain barrier cellular model.Cell reports · 2022Article
- Modelling T-cell immunity against hepatitis C virus with liver organoids in a microfluidic coculture system.Open biology · 2022Article
- IFITM protein regulation and functions: Far beyond the fight against viruses.Frontiers in immunology · 2022Review
- Characterization of RNA Sensing Pathways in Hepatoma Cell Lines and Primary Human Hepatocytes.Cells · 2021Article
- Generation of Hepatobiliary Cell Lineages from Human Induced Pluripotent Stem Cells: Applications in Disease Modeling and Drug Screening.International journal of molecular sciences · 2021Review
- The Use of Stem Cell-Derived Organoids in Disease Modeling: An Update.International journal of molecular sciences · 2021Review
- Review
- Review
- Challenges for the Applications of Human Pluripotent Stem Cell-Derived Liver Organoids.Frontiers in cell and developmental biology · 2021Review
- Mesenchymal Stem Cells and COVID-19: Cure, Prevention, and Vaccination.Stem cells international · 2021Review
- Efficient acute and chronic infection of stem cell-derived hepatocytes by hepatitis C virus.Gut · 2020Article
- Utility of Common Marmoset (Genes · 2020Review
- Human PSC-Derived Hepatocytes Express Low Levels of Viral Pathogen Recognition Receptors, but Are Capable of Mounting an Effective Innate Immune Response.International journal of molecular sciences · 2020Article
28 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Primary human hepatocytes isolated from patient biopsies represent the most physiologically relevant cell culture model for hepatitis C virus (HCV) infection, but these primary cells are not readily accessible, display individual variability, and are largely refractory to genetic manipulation. Hepatocyte-like cells differentiated from pluripotent stem cells provide an attractive alternative as they not only overcome these shortcomings but can also provide an unlimited source of noncancer cells for both research and cell therapy. Despite its promise, the permissiveness to HCV infection of differentiated human hepatocyte-like cells (DHHs) has not been explored. Here we report a novel infection model based on DHHs derived from human embryonic (hESCs) and induced pluripotent stem cells (iPSCs). DHHs generated in chemically defined media under feeder-free conditions were subjected to infection by both HCV derived in cell culture (HCVcc) and patient-derived virus (HCVser). Pluripotent stem cells and definitive endoderm were not permissive for HCV infection whereas hepatic progenitor cells were persistently infected and secreted infectious particles into culture medium. Permissiveness to infection was correlated with induction of the liver-specific microRNA-122 and modulation of cellular factors that affect HCV replication. RNA interference directed toward essential cellular cofactors in stem cells resulted in HCV-resistant hepatocyte-like cells after differentiation. The ability to infect cultured cells directly with HCV patient serum, to study defined stages of viral permissiveness, and to produce genetically modified cells with desired phenotypes all have broad significance for host-pathogen interactions and cell therapy.
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Registered trials
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.