ArticleThe Journal of clinical investigation2021
TLR3 controls constitutive IFN-β antiviral immunity in human fibroblasts and cortical neurons.
Article in The Journal of clinical investigation, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 70 papers.
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Who cites it
70 citing papers in PubMed, 97 citations in OpenAlex.
- The cell-type-specific roles of Toll-like receptors in herpes simplex virus infection and pathogenesis.Virulence · 2026Review
- Familial pulmonary alveolar proteinosis and type I interferonopathy by mutation of STAT2 (TIMS2).The Journal of experimental medicine · 2026Article
- Structural and molecular principles of DAMP biology.Nature structural & molecular biology · 2026Review
- Getting on your last nerve: IFNs and resistance to infection.Journal of immunology (Baltimore, Md. : 1950) · 2026Review
- Defective RNA Polymerase III sensing of mitochondrial DNA in pulmonary epithelial cells impairs type I IFN immunity to SARS-CoV-2.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Human interferon-ω: an underappreciated type I interferon.Frontiers in immunology · 2026Review
- Ubiquitin-specific protease 5 promotes EV-A71 replication by de-ubiquitinating MAVS and IRF3.Virologica Sinica · 2025Article
- Antiviral responses in peripheral and brain neurons.Current opinion in immunology · 2025Review
- Megakaryocytic Differentiation Regulates the Permissiveness and Antiviral Response of the Megakaryocytic Erythroid Progenitor to Dengue Virus.International journal of molecular sciences · 2025Article
- Viral-Directed Augmentation of Kupffer Cell Cross-Presentation Provokes Antitumor Immunity Against Liver Metastasis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Adeno-associated virus 2 CRISPR/Cas9-mediated targeting of hepatitis B virus in tree shrews.Virus research · 2025Article
- RIPK3 coordinates RHIM domain-dependent antiviral inflammatory transcription in neurons.Science signaling · 2025Article
- Toll-like receptor 3: a double-edged sword.Biomarker research · 2025Review
- A common form of dominant human IFNAR1 deficiency impairs IFN-α and -ω but not IFN-β-dependent immunity.The Journal of experimental medicine · 2025Article
- Inflammatory factors collaboratively linkFrontiers in immunology · 2025Review
- Targeting Trichloroethylene-Induced Renal Endothelial Cell Injuries: A Role of Poly I:C in Amplification of HMGB1 Acetylation.Journal of toxicology · 2025Article
- Interferon-stimulated gene subtypes as key indicators of immune landscape and survival outcomes in ovarian cancer.Discover oncology · 2024Article
- Single-cell RNA sequencing reveals the diversity of the immunological landscape response to genital herpes.Virologica Sinica · 2024Article
- An updated review of HSV-1 infection-associated diseases and treatment, vaccine development, and vector therapy application.Virulence · 2024Review
- Review
10 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 14 institutions in 5 countries.
Funding
Abstract
Human herpes simplex virus 1 (HSV-1) encephalitis can be caused by inborn errors of the TLR3 pathway, resulting in impairment of CNS cell-intrinsic antiviral immunity. Deficiencies of the TLR3 pathway impair cell-intrinsic immunity to vesicular stomatitis virus (VSV) and HSV-1 in fibroblasts, and to HSV-1 in cortical but not trigeminal neurons. The underlying molecular mechanism is thought to involve impaired IFN-α/β induction by the TLR3 recognition of dsRNA viral intermediates or by-products. However, we show here that human TLR3 controls constitutive levels of IFNB mRNA and secreted bioactive IFN-β protein, and thereby also controls constitutive mRNA levels for IFN-stimulated genes (ISGs) in fibroblasts. Tlr3-/- mouse embryonic fibroblasts also have lower basal ISG levels. Moreover, human TLR3 controls basal levels of IFN-β secretion and ISG mRNA in induced pluripotent stem cell-derived cortical neurons. Consistently, TLR3-deficient human fibroblasts and cortical neurons are vulnerable not only to both VSV and HSV-1, but also to several other families of viruses. The mechanism by which TLR3 restricts viral growth in human fibroblasts and cortical neurons in vitro and, by inference, by which the human CNS prevents infection by HSV-1 in vivo, is therefore based on the control of early viral infection by basal IFN-β immunity.
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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.