ArticleJournal of immunology (Baltimore, Md. : 1950)2017
Sphingosine 1-Phosphate Lyase Enhances the Activation of IKKε To Promote Type I IFN-Mediated Innate Immune Responses to Influenza A Virus Infection.
Article in Journal of immunology (Baltimore, Md. : 1950), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
18 citing papers in PubMed, 26 citations in OpenAlex.
- Article
- Review
- Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state.Advances in biological regulation · 2024Review
- Triggering Degradation of Host Cellular Proteins for Robust Propagation of Influenza Viruses.International journal of molecular sciences · 2024Review
- Single-tailed heterocyclic carboxamide lipids for macrophage immune-modulation.Biomaterials science · 2023Article
- Signaling sphingolipids are biomarkers for atopic dermatitis prone to disseminated viral infections.The Journal of allergy and clinical immunology · 2022Article
- Enzymatic independent role of sphingosine kinase 2 in regulating the expression of type I interferon during influenza A virus infection.PLoS pathogens · 2022Article
- Analyzing Opposing Interactions Between Sphingosine 1-Phosphate Lyase and Influenza A Virus.DNA and cell biology · 2022Article
- Regulation of antiviral innate immune signaling and viral evasion following viral genome sensing.Experimental & molecular medicine · 2021Review
- Wood smoke particle exposure in mice reduces the severity of influenza infection.Toxicology and applied pharmacology · 2021Article
- Review
- Influenza A virus NS1 induces degradation of sphingosine 1-phosphate lyase to obstruct the host innate immune response.Virology · 2021Article
- The roles of lipids in SARS-CoV-2 viral replication and the host immune response.Journal of lipid research · 2021Review
- Tempering Macrophage Plasticity for Controlling SARS-CoV-2 Infection for Managing COVID-19 Disease.Frontiers in pharmacology · 2020Article
- Druggable Sphingolipid Pathways: Experimental Models and Clinical Opportunities.Advances in experimental medicine and biology · 2020Review
- Emerging Connections of S1P-Metabolizing Enzymes with Host Defense and Immunity During Virus Infections.Viruses · 2019Review
- Article
- sNASP inhibits TLR signaling to regulate immune response in sepsis.The Journal of clinical investigation · 2018Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
Sphingosine 1-phosphate (S1P) lyase (SPL) is an intracellular enzyme that mediates the irreversible degradation of the bioactive lipid S1P. We have previously reported that overexpressed SPL displays anti-influenza viral activity; however, the underlying mechanism is incompletely understood. In this study, we demonstrate that SPL functions as a positive regulator of IKKε to propel type I IFN-mediated innate immune responses against viral infection. Exogenous SPL expression inhibited influenza A virus replication, which correlated with an increase in type I IFN production and IFN-stimulated gene accumulation upon infection. In contrast, the lack of SPL expression led to an elevated cellular susceptibility to influenza A virus infection. In support of this, SPL-deficient cells were defective in mounting an effective IFN response when stimulated by influenza viral RNAs. SPL augmented the activation status of IKKε and enhanced the kinase-induced phosphorylation of IRF3 and the synthesis of type I IFNs. However, the S1P degradation-incompetent form of SPL also enhanced IFN responses, suggesting that SPL's pro-IFN function is independent of S1P. Biochemical analyses revealed that SPL, as well as the mutant form of SPL, interacts with IKKε. Importantly, when endogenous IKKε was downregulated using a small interfering RNA approach, SPL's anti-influenza viral activity was markedly suppressed. This indicates that IKKε is crucial for SPL-mediated inhibition of influenza virus replication. Thus, the results illustrate the functional significance of the SPL-IKKε-IFN axis during host innate immunity against viral infection.
Indexed as
Identifiers
What OpenQuestion holds
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.