ArticleScience translational medicine2015
Interferon-λ restricts West Nile virus neuroinvasion by tightening the blood-brain barrier.
Article in Science translational medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 166 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
166 citing papers in PubMed, 1 synthesis or guideline pooled it, 221 citations in OpenAlex.
- Gene expression profiles in neurological tissues during West Nile virus infection: a critical meta-analysis.BMC genomics · 2018Pooled it
- Interferon-λ inhibits immunopathology and boosts T cell-mediated immunity in a mouse model of mucosal viral infection.The Journal of clinical investigation · 2026Article
- Powassan Virus NS5 Antagonizes TYK2-Mediated Immune Signaling Pathways.bioRxiv : the preprint server for biology · 2026Article
- Immune Evasion by Neurotropic Viruses: Molecular Strategies, Cellular Targets, and Consequences for CNS Infection.International journal of molecular sciences · 2026Review
- Characterization of an isogenicInfection and immunity · 2026Article
- West Nile Neuroinvasive Disease: Current Management, Emerging Therapies and Future Clinical Trial Priorities.Reviews in medical virology · 2026Review
- Subtype-specific functions of basal IFNλs.Journal of virology · 2026Review
- Article
- Review
- Microbiota-dependent interferon-λ controls immunity of the uterus and maternal-fetal interface.Research square · 2026Article
- Type I and III interferon responses restrict infection by tick-borne orthoflaviviruses through IFI6.Journal of virology · 2026Article
- Microbiota-dependent IFN-L controls uterine and placental immunity.bioRxiv : the preprint server for biology · 2026Article
- Interferon lambda signaling to maternal dendritic cells protects against congenital Zika virus infection.bioRxiv : the preprint server for biology · 2026Article
- Interferon-λ-neutralizing autoantibodies and common autoimmune disease autoantibodies in pediatric acute-onset neuropsychiatric syndrome.Frontiers in immunology · 2026Article
- Interplay between flaviviruses and the interferon response: mechanisms of immune evasion and therapeutic implications.Frontiers in pharmacology · 2026Review
- Pathogenic breaches: how viruses compromise blood-tissue barriers.Tissue barriers · 2026Review
- Basal IFN-λ2/3 expression mediates tight junction formation in human epithelial cells.The EMBO journal · 2025Article
- Interferons in health and disease.Cell · 2025Review
- Interferon Lambda: The Next Frontier in Antiviral Therapy?Pharmaceuticals (Basel, Switzerland) · 2025Review
- Expression and function of interferon lambda receptor 1 variants.FEBS letters · 2025Review
106 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
- Erratum issued
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
Although interferon-λ [also known as type III interferon or interleukin-28 (IL-28)/IL-29] restricts infection by several viruses, its inhibitory mechanism has remained uncertain. We used recombinant interferon-λ and mice lacking the interferon-λ receptor (IFNLR1) to evaluate the effect of interferon-λ on infection with West Nile virus, an encephalitic flavivirus. Cell culture studies in mouse keratinocytes and dendritic cells showed no direct antiviral effect of exogenous interferon-λ, even though expression of interferon-stimulated genes was induced. We observed no differences in West Nile virus burden between wild-type and Ifnlr1(-/-) mice in the draining lymph nodes, spleen, or blood. We detected increased West Nile virus infection in the brain and spinal cord of Ifnlr1(-/-) mice, yet this was not associated with a direct antiviral effect in mouse neurons. Instead, we observed an increase in blood-brain barrier permeability in Ifnlr1(-/-) mice. Treatment of mice with pegylated interferon-λ2 resulted in decreased blood-brain barrier permeability, reduced West Nile virus infection in the brain without affecting viremia, and improved survival against lethal virus challenge. An in vitro model of the blood-brain barrier showed that interferon-λ signaling in mouse brain microvascular endothelial cells increased transendothelial electrical resistance, decreased virus movement across the barrier, and modulated tight junction protein localization in a protein synthesis- and signal transducer and activator of transcription 1 (STAT1)-independent manner. Our data establish an indirect antiviral function of interferon-λ in which noncanonical signaling through IFNLR1 tightens the blood-brain barrier and restricts viral neuroinvasion and pathogenesis.
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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.