ArticleThe Journal of allergy and clinical immunology2011
NEMO is a key component of NF-κB- and IRF-3-dependent TLR3-mediated immunity to herpes simplex virus.
Article in The Journal of allergy and clinical immunology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 85 citations in OpenAlex.
- Host Genetic Susceptibility and Antiviral Immunity Shape the Pathogenesis and Outcomes of Herpes Simplex Encephalitis.Biology · 2026Review
- Autoantibodies neutralizing type I IFNs in patients with fulminant herpes simplex virus hepatitis.The Journal of experimental medicine · 2026Article
- Association of Haematological Parameters With TLR Genes in Healthy and Distemper-Infected Dogs Haematology and TLRs in Distemper.Veterinary medicine and science · 2026Article
- Role for NF-κB in herpes encephalitis pathology in mice genocopying an inborn error of IRF3-IFN immunity.The Journal of experimental medicine · 2026Article
- The cell-mediated adaptive immune response to herpes simplex virus type 1 encephalitis: mechanisms and clinical implications.Frontiers in immunology · 2026Review
- The immunogenetic basis of severe herpes simplex infections in neonates and children: a review.Pediatric research · 2025Review
- The monogenic landscape of human infectious diseases.The Journal of allergy and clinical immunology · 2025Review
- Review
- Mutations disrupting the kinase domain of IKKα lead to immunodeficiency and immune dysregulation in humans.The Journal of experimental medicine · 2025Article
- Review
- Orchestration of antiviral responses within the infected central nervous system.Cellular & molecular immunology · 2024Review
- Article
- Oxymatrine Modulation of TLR3 Signaling: A Dual-Action Mechanism for H9N2 Avian Influenza Virus Defense and Immune Regulation.Molecules (Basel, Switzerland) · 2024Article
- USP10 regulates macrophage inflammation responses via stabilizing NEMO in LPS-induced sepsis.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2023Article
- Inborn Errors of Immunity Predisposing to Herpes Simplex Virus Infections of the Central Nervous System.Pathogens (Basel, Switzerland) · 2023Review
- Unlocking life-threatening COVID-19 through two types of inborn errors of type I IFNs.The Journal of clinical investigation · 2023Review
- RIPK3 and caspase 8 collaborate to limit herpes simplex encephalitis.PLoS pathogens · 2022Article
- Review
- Genetically programmed alternative splicing of NEMO mediates an autoinflammatory disease phenotype.The Journal of clinical investigation · 2022Article
- Disrupting Neurons and Glial Cells Oneness in the Brain-The Possible Causal Role of Herpes Simplex Virus Type 1 (HSV-1) in Alzheimer's Disease.International journal of molecular sciences · 2021Review
Corrections and comments
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Authors and funding
16 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundChildren with germline mutations in Toll-like receptor 3 (TLR3), UNC93B1, TNF receptor-associated factor 3, and signal transducer and activator of transcription 1 are prone to herpes simplex virus-1 encephalitis, owing to impaired TLR3-triggered, UNC-93B-dependent, IFN-α/β, and/or IFN-λ-mediated signal transducer and activator of transcription 1-dependent immunity.
objectiveWe explore here the molecular basis of the pathogenesis of herpes simplex encephalitis in a child with a hypomorphic mutation in nuclear factor-κB (NF-κB) essential modulator, which encodes the regulatory subunit of the inhibitor of the Iκβ kinase complex.
methodsThe TLR3 signaling pathway was investigated in the patient's fibroblasts by analyses of IFN-β, IFN-λ, and IL-6 mRNA and protein levels, by quantitative PCR and ELISA, respectively, upon TLR3 stimulation (TLR3 agonists or TLR3-dependent viruses). NF-κB activation was assessed by electrophoretic mobility shift assay and interferon regulatory factor 3 dimerization on native gels after stimulation with a TLR3 agonist.
resultsThe patient's fibroblasts displayed impaired responses to TLR3 stimulation in terms of IFN-β, IFN-λ, and IL-6 production, owing to impaired activation of both NF-κB and IRF-3. Moreover, vesicular stomatitis virus, a potent IFN-inducer in human fibroblasts, and herpes simplex virus-1, induced only low levels of IFN-β and IFN-λ in the patient's fibroblasts, resulting in enhanced viral replication and cell death, as reported for UNC-93B-deficient fibroblasts.
conclusionHerpes simplex encephalitis may occur in patients carrying NF-κB essential modulator mutations, due to the impairment of NF-κB- and interferon regulatory factor 3-dependent-TLR3-mediated antiviral IFN production.
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