ArticleThe EMBO journal2013
Interferon lambda 4 signals via the IFNλ receptor to regulate antiviral activity against HCV and coronaviruses.
Article in The EMBO journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 122 papers, 1 of them a synthesis that pooled it.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
122 citing papers in PubMed, 1 synthesis or guideline pooled it, 193 citations in OpenAlex.
- The potential of IFN-λ, IL-32γ, IL-6, and IL-22 as safeguards against human viruses: a systematic review and a meta-analysis.Frontiers in immunology · 2024Pooled it
- Interferon-λ4 is a cell-autonomous type III interferon associated with pre-treatment hepatitis C virus burden.Virology · 2015Trial
- IFNL4-ΔG genotype is associated with slower viral clearance in hepatitis C, genotype-1 patients treated with sofosbuvir and ribavirin.The Journal of infectious diseases · 2014Trial
- 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
- Differential host responses by the type I and III interferons in primary differentiated human nasal epithelial cells are a determinant of antiviral activity.Frontiers in pharmacology · 2026Article
- Expression and function of interferon lambda receptor 1 variants.FEBS letters · 2025Review
- Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.Nature communications · 2025Article
- JAK-STAT pathway, type I/II cytokines, and new potential therapeutic strategy for autoimmune bullous diseases: update on pemphigus vulgaris and bullous pemphigoid.Frontiers in immunology · 2025Review
- Reduced IFNL1 and/or IFNL2, but not IFNL3 is associated with worse outcome in patients with COVID-19.Clinical and experimental immunology · 2024Article
- Interferon lambda 4 is a gut antimicrobial protein.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Context-specific anti-inflammatory roles of type III interferon signaling in the lung in nonviral injuries.Physiological reports · 2024Article
- In search of a function for human type III interferons: insights from inherited and acquired deficits.Current opinion in immunology · 2024Review
- IFN-λ3 is induced byInfection and immunity · 2024Article
- A Novel Inactive Isoform with a Restored Reading Frame Is Expressed from the Human Interferon Lambda 4 TT Allele at rs368234815.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- The Interferon-Lambda Family Celebrates 20 Years of Scientific Discovery.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Enhanced soluble expression of active recombinant human interleukin-29 using champion pET SUMO system.Biotechnology letters · 2023Article
- Current Landscape of IFN-λ: Induction, Inhibition, and Potential Clinical Applications to Treat Respiratory Viral Infections.ImmunoHorizons · 2023Article
- Influence of Canonical and Non-Canonical IFNLR1 Isoform Expression on Interferon Lambda Signaling.Viruses · 2023Article
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The IFNL4 gene is a recently discovered type III interferon, which in a significant fraction of the human population harbours a frameshift mutation abolishing the IFNλ4 ORF. The expression of IFNλ4 is correlated with both poor spontaneous clearance of hepatitis C virus (HCV) and poor response to treatment with type I interferon. Here, we show that the IFNL4 gene encodes an active type III interferon, named IFNλ4, which signals through the IFNλR1 and IL-10R2 receptor chains. Recombinant IFNλ4 is antiviral against both HCV and coronaviruses at levels comparable to IFNλ3. However, the secretion of IFNλ4 is impaired compared to that of IFNλ3, and this impairment is not due to a weak signal peptide, which was previously believed. We found that IFNλ4 gets N-linked glycosylated and that this glycosylation is required for secretion. Nevertheless, this glycosylation is not required for activity. Together, these findings result in the paradox that IFNλ4 is strongly antiviral but a disadvantage during HCV infection.
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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.