ArticleNature2012
Impaired intrinsic immunity to HSV-1 in human iPSC-derived TLR3-deficient CNS cells.
Article in Nature, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 211 papers.
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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.
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Who cites it
211 citing papers in PubMed, 330 citations in OpenAlex.
- The cell-type-specific roles of Toll-like receptors in herpes simplex virus infection and pathogenesis.Virulence · 2026Review
- Host Genetic Susceptibility and Antiviral Immunity Shape the Pathogenesis and Outcomes of Herpes Simplex Encephalitis.Biology · 2026Review
- Clinical and immunological characterization of a child with a homozygous TBK1 kinase-domain truncation.Immunologic research · 2026Article
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- Toward a monogenic architecture of human infections: From 1996 to 2026.Journal of human immunity · 2026Review
- STING agonists as antiviral agents.FEBS letters · 2026Review
- Optimization of lytic herpes simplex virus infection in human induced pluripotent stem cell-derived cortical neurones.The Journal of general virology · 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
- Antiviral responses in peripheral and brain neurons.Current opinion in immunology · 2025Review
- A Comprehensive Review of poly(I: C) as a Tool for Investigating Astrocytic TLR3 Signaling.Neurochemical research · 2025Review
- Cell reprogramming: methods, mechanisms and applications.Cell regeneration (London, England) · 2025Review
- Tackling cutaneous herpes simplex virus disease with topical immunomodulators-a call to action.Clinical microbiology reviews · 2025Review
- Overview of dendritic cells subsets and their involvement in immune-related pathological disease.BioImpacts : BI · 2025Review
- Catch me if you can: viral nucleic acids to host sensors.Frontiers in immunology · 2025Review
- An updated review of HSV-1 infection-associated diseases and treatment, vaccine development, and vector therapy application.Virulence · 2024Review
- Review
- Orchestration of antiviral responses within the infected central nervous system.Cellular & molecular immunology · 2024Review
- Article
- Herpes simplex encephalitis due to a mutation in an E3 ubiquitin ligase.Nature communications · 2024Article
151 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
23 authors at 13 institutions in 4 countries.
Funding
Abstract
In the course of primary infection with herpes simplex virus 1 (HSV-1), children with inborn errors of toll-like receptor 3 (TLR3) immunity are prone to HSV-1 encephalitis (HSE). We tested the hypothesis that the pathogenesis of HSE involves non-haematopoietic CNS-resident cells. We derived induced pluripotent stem cells (iPSCs) from the dermal fibroblasts of TLR3- and UNC-93B-deficient patients and from controls. These iPSCs were differentiated into highly purified populations of neural stem cells (NSCs), neurons, astrocytes and oligodendrocytes. The induction of interferon-β (IFN-β) and/or IFN-λ1 in response to stimulation by the dsRNA analogue polyinosinic:polycytidylic acid (poly(I:C)) was dependent on TLR3 and UNC-93B in all cells tested. However, the induction of IFN-β and IFN-λ1 in response to HSV-1 infection was impaired selectively in UNC-93B-deficient neurons and oligodendrocytes. These cells were also much more susceptible to HSV-1 infection than control cells, whereas UNC-93B-deficient NSCs and astrocytes were not. TLR3-deficient neurons were also found to be susceptible to HSV-1 infection. The rescue of UNC-93B- and TLR3-deficient cells with the corresponding wild-type allele showed that the genetic defect was the cause of the poly(I:C) and HSV-1 phenotypes. The viral infection phenotype was rescued further by treatment with exogenous IFN-α or IFN-β ( IFN-α/β) but not IFN-λ1. Thus, impaired TLR3- and UNC-93B-dependent IFN-α/β intrinsic immunity to HSV-1 in the CNS, in neurons and oligodendrocytes in particular, may underlie the pathogenesis of HSE in children with TLR3-pathway deficiencies.
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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.