ArticleGastroenterology2012
HCV infection induces a unique hepatic innate immune response associated with robust production of type III interferons.
Article in Gastroenterology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 150 papers.
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Who cites it
150 citing papers in PubMed, 262 citations in OpenAlex.
- Peripheral blood correlates of virologic relapse after Sofosbuvir and Ribavirin treatment of Genotype-1 HCV infection.BMC infectious diseases · 2020Trial
- 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
- Endogenous intrahepatic IFNs and association with IFN-free HCV treatment outcome.The Journal of clinical investigation · 2014Trial
- Temperature rise after peginterferon alfa-2a injection in patients with chronic hepatitis C is associated with virological response and is modulated by IL28B genotype.Journal of hepatology · 2013Trial
- Plasma interferon-gamma-inducible protein-10 (IP-10) levels during acute hepatitis C virus infection.Hepatology (Baltimore, Md.) · 2013Trial
- Function of Interferon Lambda Receptor 1 Variants in Stem Cell-Derived Hepatocytes with Abrogated EndogenousJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2025Article
- Review
- Article
- HCV treatment outcome depends on SNPs of IFNL3-Gene polymorphisms (rs12979860) and cirrhotic changes in liver parenchyma.Heliyon · 2023Article
- Physiomimetic In Vitro Human Models for Viral Infection in the Liver.Seminars in liver disease · 2023Review
- Downregulation of SOCS1 increases interferon-induced ISGylation during differentiation of induced-pluripotent stem cells to hepatocytes.JHEP reports : innovation in hepatology · 2022Article
- [Mechanism and clinical significance of HBV reactivation after anti-HCV therapy].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2022Review
- The Human Liver-Expressed Lectin CD302 Restricts Hepatitis C Virus Infection.Journal of virology · 2022Article
- Galectin-9 restricts hepatitis B virus replication via p62/SQSTM1-mediated selective autophagy of viral core proteins.Nature communications · 2022Article
- Antiviral Toll-like Receptor Signaling in Non-Parenchymal Liver Cells Is Restricted to TLR3.Viruses · 2022Article
- RegEnrich gene regulator enrichment analysis reveals a key role of the ETS transcription factor family in interferon signaling.Communications biology · 2022Article
- Dual roles and potential applications of exosomes in HCV infections.Frontiers in microbiology · 2022Review
- Possible relationship between IL28B rs12979860 and TLR2 -196 to -174 del/ins polymorphisms and the liver fibrosis stage in hepatitis C patients.Archives of virology · 2022Article
- Innate immunity in hepatitis B and D virus infection: consequences for viral persistence, inflammation, and T cell recognition.Seminars in immunopathology · 2021Review
- Initial HCV infection of adult hepatocytes triggers a temporally structured transcriptional program containing diverse pro- and anti-viral elements.Journal of virology · 2021Article
90 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsPolymorphisms in the IL28B gene have been associated with clearance of hepatitis C virus (HCV), indicating a role for type III interferons (IFNs) in HCV infection. Little is known about the function of type III IFNs in intrinsic antiviral innate immunity.
methodsWe used in vivo and in vitro models to characterize the role of the type III IFNs in HCV infection and analyzed gene expression in liver biopsy samples from HCV-infected chimpanzees and patients. Messenger RNA and protein expression were studied in HCV-infected hepatoma cell lines and primary human hepatocytes.
resultsHCV infection of primary human hepatocytes induced production of chemokines and type III IFNs, including interleukin (IL)-28, and led to expression of IFN-stimulated genes (ISGs). Chimpanzees infected with HCV showed rapid induction of hepatic type III IFN, associated with up-regulation of ISGs and minimal induction of type I IFNs. In liver biopsy specimens from HCV-infected patients, hepatic expression of IL-28 correlated with levels of ISGs but not of type I IFNs. HCV infection produced extensive changes with gene expression in addition to ISGs in primary human hepatocytes. The induction of type III IFNs is regulated by IFN regulatory factor 3 and nuclear factor κB. Type III IFNs up-regulate ISGs with a different kinetic profile than type 1 IFNs and induce a distinct set of genes, which might account for their functional differences.
conclusionsHCV infection results predominantly in induction of type III IFNs in livers of humans and chimpanzees; the level of induction correlates with hepatic levels of ISGs. These findings might account for the association among IL-28, level of ISGs, and recovery from HCV infection and provide a therapeutic strategy for patients who do not respond to IFN 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.