ArticleThe Journal of experimental medicine2016
Interferon lambda 4 expression is suppressed by the host during viral infection.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 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
44 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 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
- Association of IFNλ4 rs12979860 polymorphism with the acquisition of HCV and HIV infections among people who inject drugs.Journal of medical virology · 2018Trial
- Impact of Interferon Lambda 4 Genotype on Interferon-Stimulated Gene Expression During Direct-Acting Antiviral Therapy for Hepatitis C.Hepatology (Baltimore, Md.) · 2018Trial
- Subtype-specific functions of basal IFNλs.Journal of virology · 2026Review
- Lineage-specific chromatin poising enforced by ETS-IRF composite elements determines the divergent interferon responses of plasmacytoid dendritic cells and epithelial cells.bioRxiv : the preprint server for biology · 2026Article
- 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
- Interferon lambda 4 is a gut antimicrobial protein.Proceedings of the National Academy of Sciences of the United States of America · 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
- Autoantibodies Neutralizing Type III Interferons Are Uncommon in Patients with Severe Coronavirus Disease 2019 Pneumonia.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2023Article
- Current Landscape of IFN-λ: Induction, Inhibition, and Potential Clinical Applications to Treat Respiratory Viral Infections.ImmunoHorizons · 2023Article
- Adaptive Evolution of the OAS Gene Family Provides New Insights into the Antiviral Ability of Laurasiatherian Mammals.Animals : an open access journal from MDPI · 2023Article
- Distinct molecular phenotypes involving several human diseases are induced by IFN-λ3 and IFN-λ4 in monocyte-derived macrophages.Genes and immunity · 2022Article
- Macrophages and neutrophils express IFNλs in granulomas fromFrontiers in immunology · 2022Article
- RNA regulatory mechanisms that control antiviral innate immunity.Immunological reviews · 2021Review
- Interferon lambda 4 impairs hepatitis C viral antigen presentation and attenuates T cell responses.Nature communications · 2021Article
- Review
- Functional genetic variants of the IFN-λ3 (IL28B) gene and transcription factor interactions on its promoter.Cytokine · 2021Article
- Viral infections in humans and mice with genetic deficiencies of the type I IFN response pathway.European journal of immunology · 2021Review
- 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
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
Abstract
Interferon (IFN) lambdas are critical antiviral effectors in hepatic and mucosal infections. Although IFNλ1, IFNλ2, and IFNλ3 act antiviral, genetic association studies have shown that expression of the recently discovered IFNL4 is detrimental to hepatitis C virus (HCV) infection through a yet unknown mechanism. Intriguingly, human IFNL4 harbors a genetic variant that introduces a premature stop codon. We performed a molecular and biochemical characterization of IFNλ4 to determine its role and regulation of expression. We found that IFNλ4 exhibits similar antiviral activity to IFNλ3 without negatively affecting antiviral IFN activity or cell survival. We show that humans deploy several mechanisms to limit expression of functional IFNλ4 through noncoding splice variants and nonfunctional protein isoforms. Furthermore, protein-coding IFNL4 mRNA are not loaded onto polyribosomes and lack a strong polyadenylation signal, resulting in poor translation efficiency. This study provides mechanistic evidence that humans suppress IFNλ4 expression, suggesting that immune function is dependent on other IFNL family members.
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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.