ArticleGastroenterology2015
Hepatitis C virus infection induces autocrine interferon signaling by human liver endothelial cells and release of exosomes, which inhibits viral replication.
Article in Gastroenterology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 74 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
74 citing papers in PubMed, 106 citations in OpenAlex.
- Liver sinusoidal endothelial cells (LSECs) modifications in patients with chronic hepatitis C.Scientific reports · 2019Trial
- Hepatitis C Virus Sensing by Human Trophoblasts Induces Innate Immune Responses and Recruitment of Maternal NK Cells: Potential Implications for Limiting Vertical Transmission.Journal of immunology (Baltimore, Md. : 1950) · 2015Trial
- Liver sinusoidal endothelial cells in liver diseases and hepatocellular carcinoma: molecular mechanisms, physiology, and therapies.Molecular biomedicine · 2026Review
- Viperin suppresses goose astrovirus type 2 replication through inhibition of viral RdRP activity.Veterinary research · 2026Article
- Leptospiral dissemination is restrained by liver macrophages through Clec4d-driven capture via C/EBPβ activation.PLoS pathogens · 2026Article
- Viperin: A Multifunctional Protein in Antiviral Immunity and Disease Pathogenesis.Pathogens (Basel, Switzerland) · 2025Review
- Review
- Crucial Roles of RSAD2/viperin in Immunomodulation, Mitochondrial Metabolism and Autoimmune Diseases.Inflammation · 2025Review
- Extracellular Vesicles in Viral Liver Diseases.Viruses · 2024Review
- Lipid droplets in pathogen infection and host immunity.Acta pharmacologica Sinica · 2024Review
- Extracellular Vesicles inInternational journal of molecular sciences · 2024Review
- Engineered small extracellular vesicles as a novel platform to suppress human oncovirus-associated cancers.Infectious agents and cancer · 2023Review
- Role of Extracellular Vesicles in Liver Diseases.Life (Basel, Switzerland) · 2023Review
- Contribution of Hepatic Steatosis-Intensified Extracellular Vesicle Release to Aggravated Inflammatory Endothelial Injury in Liver-Specific Asah1 Gene Knockout Mice.The American journal of pathology · 2023Article
- Physiomimetic In Vitro Human Models for Viral Infection in the Liver.Seminars in liver disease · 2023Review
- Article
- Pathological Contribution of Extracellular Vesicles and Their MicroRNAs to Progression of Chronic Liver Disease.Biology · 2022Review
- Circulating cell-specific extracellular vesicles as biomarkers for the diagnosis and monitoring of chronic liver diseases.Cellular and molecular life sciences : CMLS · 2022Review
- Neuronal-enriched extracellular vesicles in individuals with IBS: A pilot study of COMT and BDNF.Neurogastroenterology and motility · 2022Article
- Dual roles and potential applications of exosomes in HCV infections.Frontiers in microbiology · 2022Review
14 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
17 authors at 7 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsLiver sinusoidal endothelial cells (LSECs) make up a large proportion of the nonparenchymal cells in the liver. LSECs are involved in induction of immune tolerance, but little is known about their functions during hepatitis C virus (HCV) infection.
methodsPrimary human LSECs (HLSECs) and immortalized liver endothelial cells (TMNK-1) were exposed to various forms of HCV, including full-length transmitted/founder virus, sucrose-purified Japanese fulminant hepatitis-1 (JFH-1), a virus encoding a luciferase reporter, and the HCV-specific pathogen-associated molecular pattern molecules. Cells were analyzed by confocal immunofluorescence, immunohistochemical, and polymerase chain reaction assays.
resultsHLSECs internalized HCV, independent of cell-cell contacts; HCV RNA was translated but not replicated. Through pattern recognition receptors (Toll-like receptor 7 and retinoic acid-inducible gene 1), HCV RNA induced consistent and broad transcription of multiple interferons (IFNs); supernatants from primary HLSECs transfected with HCV-specific pathogen-associated molecular pattern molecules increased induction of IFNs and IFN-stimulated genes in HLSECs. Recombinant type I and type III IFNs strongly up-regulated HLSEC transcription of IFN λ3 (IFNL3) and viperin (RSAD2), which inhibit replication of HCV. Compared with CD8(+) T cells, HLSECs suppressed HCV replication within Huh7.5.1 cells, also inducing IFN-stimulated genes in co-culture. Conditioned media from IFN-stimulated HLSECs induced expression of antiviral genes by uninfected primary human hepatocytes. Exosomes, derived from HLSECs after stimulation with either type I or type III IFNs, controlled HCV replication in a dose-dependent manner.
conclusionsCultured HLSECs produce factors that mediate immunity against HCV. HLSECs induce self-amplifying IFN-mediated responses and release of exosomes with antiviral activity.
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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.