ArticleScientific reports2017
IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Targets of protective immunity and opportunities in hepatitis C virus vaccine development.Nature reviews. Immunology · 2026Review
- IFN-λ4 Exhibits Differential Induction and Antiviral Activity in RSV and HMPV Infections.Viruses · 2026Article
- MERS-CoV and SARS-CoV-1 proteins inhibit the IFN-α JAK/STAT pathway of epithelial cells, via IFN-λ-induced USP18.Frontiers in immunology · 2026Article
- Interferon levels and interferon-stimulated gene expression identify patient subsets with distinct clinical and immunological characteristics in systemic lupus erythematosus.Frontiers in immunology · 2026Article
- Roles of ubiquitin-specific proteases in inflammatory diseases.Frontiers in immunology · 2024Review
- Impact of COVID-19 on epidemic trend of hepatitis C in Henan Province assessed by interrupted time series analysis.BMC infectious diseases · 2023Article
- The signal-to-cutoff ratios to predict HCV infection among people who inject drugs.Virusdisease · 2022Article
- Inhibition of the IFN-α JAK/STAT Pathway by MERS-CoV and SARS-CoV-1 Proteins in Human Epithelial Cells.Viruses · 2022Article
- Immunological Mechanisms for Hepatocellular Carcinoma Risk after Direct-Acting Antiviral Treatment of Hepatitis C Virus Infection.Journal of clinical medicine · 2021Review
- A Role of Variance in Interferon Genes to Disease Severity in COVID-19 Patients.Frontiers in genetics · 2021Review
- Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.Frontiers in immunology · 2021Article
- The influence of interferon-lambda on restricting Middle East Respiratory Syndrome Coronavirus replication in the respiratory epithelium.Antiviral research · 2020Article
- Disentangling molecular mechanisms regulating sensitization of interferon alpha signal transduction.Molecular systems biology · 2020Article
- Interferon Response in Hepatitis C Virus-Infected Hepatocytes: Issues to Consider in the Era of Direct-Acting Antivirals.International journal of molecular sciences · 2020Review
- Review
- Structure-based glycoengineering of interferon lambda 4 enhances its productivity and anti-viral potency.Cytokine · 2020Article
- Genetics of the Human Interferon Lambda Region.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2019Review
- Revisiting the Paradox of Interferon-Stimulated Gene Expression as a Predictor of Hepatitis C Virus Treatment Response, a Decade Later.Hepatology (Baltimore, Md.) · 2018Article
- Natural Killer Cell Dysfunction in Hepatocellular Carcinoma: Pathogenesis and Clinical Implications.International journal of molecular sciences · 2018Review
- Interferon-free treatment for hepatitis C virus infection induces normalization of extrahepatic type I interferon signaling.Clinical and molecular hepatology · 2018Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic polymorphisms in IFNL4 have been shown to predict responses to IFN-α-based therapy in hepatitis C virus (HCV)-infected patients. The IFNL4-ΔG genotype, which encodes functional IFN-λ4 protein, is associated with a poor treatment response. In the present study, we investigated the induction and biological effects of IFN-λ4 in HCV-infected hepatocytes and their association with responsiveness to IFN-α. We also studied the effects of direct-acting antiviral (DAA) treatment on IFN-λ4 expression and IFN-α responsiveness. HCV infection induced IFN-λ4 expression at mRNA and protein levels in primary human hepatocytes (PHHs). In hepatoma cells, IFNL4 gene transfection or recombinant IFN-λ4 protein treatment robustly increased the protein levels of ISG15 and USP18 in an IFNLR1-dependent manner and potently blocked IFN-α signalling. The ISG15/USP18-mediated IFN-α unresponsiveness was demonstrated by transfection of siRNAs targeting ISG15 and/or USP18. This potent IFN-λ4 effect was related to prolonged ISG expression after IFNL4 gene transfection. DAA treatment of HCV-infected PHHs reduced the expression of IFN-λs, including IFN-λ4, and restored IFN-α responsiveness. These results demonstrate that virus-induced IFN-λ4 potently blocks IFN-α signalling by inducing high protein levels of ISG15 and USP18. Moreover, the data clearly demonstrate that DAA therapy restores IFN-α responsiveness in HCV-infected cells.
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