ArticleJournal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research2015
Expression of Interferon Lambda 4 Is Associated with Reduced Proliferation and Increased Cell Death in Human Hepatic Cells.
Article in Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed, 37 citations in OpenAlex.
- Achieving sustained virologic response after interferon-free hepatitis C virus treatment correlates with hepatic interferon gene expression changes independent of cirrhosis.Journal of viral hepatitis · 2016Trial
- Interferon lambda in anti-viral defense and cancer: dual roles, mechanism and therapeutic potential.Journal of translational medicine · 2026Review
- miR-194-5p targets SOCS2 to predict pegIFNα treatment response in HBeAg-positive chronic hepatitis B patients.Virology journal · 2026Article
- IFN-λ4 Exhibits Differential Induction and Antiviral Activity in RSV and HMPV Infections.Viruses · 2026Article
- Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.Nature communications · 2025Article
- Current Landscape of IFN-λ: Induction, Inhibition, and Potential Clinical Applications to Treat Respiratory Viral Infections.ImmunoHorizons · 2023Article
- Interferon lambda 4 impairs hepatitis C viral antigen presentation and attenuates T cell responses.Nature communications · 2021Article
- Expression of Interferons Lambda 3 and 4 Induces Identical Response in Human Liver Cell Lines Depending Exclusively on Canonical Signaling.International journal of molecular sciences · 2021Article
- Intracellular Accumulation of IFN-λ4 Induces ER Stress and Results in Anti-Cirrhotic but Pro-HCV Effects.Frontiers in immunology · 2021Article
- Double-edged effects of interferons on the regulation of cancer-immunity cycle.Oncoimmunology · 2021Review
- Interferon Response in Hepatitis C Virus-Infected Hepatocytes: Issues to Consider in the Era of Direct-Acting Antivirals.International journal of molecular sciences · 2020Review
- 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
- Interferon Lambda: An Immune System Factor That Cancer Epidemiologists Should Consider.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2019Article
- The IFN-λ4 Conundrum: When a Good Interferon Goes Bad.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2019Review
- IFN-λ4 Attenuates Antiviral Responses by Enhancing Negative Regulation of IFN Signaling.Journal of immunology (Baltimore, Md. : 1950) · 2017Article
- IFN-λ4 potently blocks IFN-α signalling by ISG15 and USP18 in hepatitis C virus infection.Scientific reports · 2017Article
- IFN-λ3, not IFN-λ4, likely mediates IFNL3-IFNL4 haplotype-dependent hepatic inflammation and fibrosis.Nature genetics · 2017Article
- The Role of Type III Interferons in Hepatitis C Virus Infection and Therapy.Journal of immunology research · 2017Review
- Interferon lambda 4 expression is suppressed by the host during viral infection.The Journal of experimental medicine · 2016Article
- A multifaceted computational report on the variants effect on KIR2DL3 and IFNL3 candidate gene in HCV clearance.Molecular biology reports · 2016Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Interferon lambda 4 (IFN-λ4) is a novel type-III interferon that can be generated only in individuals carrying a ΔG frame-shift allele of an exonic genetic variant (rs368234815-ΔG/TT). The rs368234815-ΔG allele is strongly associated with decreased clearance of hepatitis C virus (HCV) infection. Here, we further explored the biological function of IFN-λ4 expressed in human hepatic cells-a hepatoma cell line HepG2 and fresh primary human hepatocytes (PHHs). We performed live confocal imaging, cell death and proliferation assays, mRNA expression profiling, protein detection, and antibody blocking assays using transient and inducible stable in vitro systems. Not only did we observe significant intracellular retention of IFN-λ4 but also detected secreted IFN-λ4 in the culture media of expressing cells. Secreted IFN-λ4 induced strong activation of the interferon-stimulated genes (ISGs) in IFN-λ4-expressing and surrounding cells in transwell assays. Specifically, in PHHs, secreted IFN-λ4 induced expression of the CXCL10 transcript and a corresponding pro-inflammatory chemokine, IP-10. In IFN-λ4-expressing HepG2 cells, we also observed decreased proliferation and increased cell death. All IFN-λ4-induced phenotypes--activation of ISGs, decreased proliferation, and increased cell death--could be inhibited by an anti-IFN-λ4-specific antibody. Our study offers new insights into biology of IFN-λ4 and its possible role in HCV clearance.
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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.