ArticleNature2013
Completion of the entire hepatitis C virus life cycle in genetically humanized mice.
Article in Nature, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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
135 citing papers in PubMed, 220 citations in OpenAlex.
- Enhanced virus-specific CD8+ T cell responses by Listeria monocytogenes-infected dendritic cells in the context of Tim-3 blockade.PloS one · 2014Trial
- The Role of Human Viral Entry Receptor Mouse Models in Advancing Antiviral Antibodies and Vaccines.Vaccines · 2026Review
- Hepatitis C virus inhibits the E2F2/PI3K/AKT signaling pathway through miR-378b and leads to glycolipid metabolism disorders in the liver.Molecular biology reports · 2026Article
- Generation of a HiBiT-expressing recombinant rat hepacivirus supporting both in vivo and in vitro infection.PLoS pathogens · 2026Article
- Assessment of hepatitis C virus permissiveness in iteratively genetically humanized mice.Journal of virology · 2025Article
- Receptor transporter protein 4 (RTP4)-mediated repression of hepatitis C virus replication in mouse cells.PLoS pathogens · 2025Article
- Review: radiotherapy-mediated B cells within the TLS influence the tumor microenvironment.Journal for immunotherapy of cancer · 2025Review
- Adapted hepatitis C virus clone infects innate immunity-deficient mouse hepatocytes with minimal human HCV entry factors.JHEP reports : innovation in hepatology · 2025Article
- Review
- The Cyclophilin Inhibitor Rencofilstat Decreases HCV-Induced Hepatocellular Carcinoma Independently of Its Antiviral Activity.Viruses · 2023Article
- Mouse Liver-Expressed Shiftless Is an Evolutionarily Conserved Antiviral Effector Restricting Human and Murine Hepaciviruses.Microbiology spectrum · 2023Article
- Modeling the Tumor Microenvironment and Cancer Immunotherapy in Next-Generation Humanized Mice.Cancers · 2023Review
- Immune inactivation by neuropilin-1 predicts clinical outcome and therapeutic benefit in muscle-invasive bladder cancer.Cancer immunology, immunotherapy : CII · 2022Article
- Repurposing of cyclophilin A inhibitors as broad-spectrum antiviral agents.Drug discovery today · 2022Review
- Liver-humanized mice: A translational strategy to study metabolic disorders.Journal of cellular physiology · 2022Review
- Entry Inhibitors of Hepatitis C Virus.Advances in experimental medicine and biology · 2022Article
- Intra-host analysis of hepaciviral glycoprotein evolution reveals signatures associated with viral persistence and clearance.Virus evolution · 2022Article
- Imaging Flow Cytometry and Confocal Immunofluorescence Microscopy of Virus-Host Cell Interactions.Frontiers in cellular and infection microbiology · 2021Review
- Advances in Transgenic Mouse Models to Study Infections by Human Pathogenic Viruses.International journal of molecular sciences · 2020Review
- Liver-expressedScience advances · 2020Article
75 more citing papers are in PubMed but not listed here.
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Authors and funding
14 authors at 5 institutions in 3 countries.
Funding
Abstract
More than 130 million people worldwide chronically infected with hepatitis C virus (HCV) are at risk of developing severe liver disease. Antiviral treatments are only partially effective against HCV infection, and a vaccine is not available. Development of more efficient therapies has been hampered by the lack of a small animal model. Building on the observation that CD81 and occludin (OCLN) comprise the minimal set of human factors required to render mouse cells permissive to HCV entry, we previously showed that transient expression of these two human genes is sufficient to allow viral uptake into fully immunocompetent inbred mice. Here we demonstrate that transgenic mice stably expressing human CD81 and OCLN also support HCV entry, but innate and adaptive immune responses restrict HCV infection in vivo. Blunting antiviral immunity in genetically humanized mice infected with HCV results in measurable viraemia over several weeks. In mice lacking the essential cellular co-factor cyclophilin A (CypA), HCV RNA replication is markedly diminished, providing genetic evidence that this process is faithfully recapitulated. Using a cell-based fluorescent reporter activated by the NS3-4A protease we visualize HCV infection in single hepatocytes in vivo. Persistently infected mice produce de novo infectious particles, which can be inhibited with directly acting antiviral drug treatment, thereby providing evidence for the completion of the entire HCV life cycle in inbred mice. This genetically humanized mouse model opens new opportunities to dissect genetically HCV infection in vivo and provides an important preclinical platform for testing and prioritizing drug candidates and may also have utility for evaluating vaccine efficacy.
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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.