title: A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy.
abstract: Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and mediate the activation of NF-kappaB and the production of proinflammatory cytokines, which is critical for the innate immune system. TLR3 recognizes both double-stranded RNA and the influenza A virus. Since influenza-associated encephalopathy is frequent in Japan and East Asia and its pathological mechanism remains unknown, we analyzed several genes including TLRs and the retinoic acid inducible gene I, which could be involved in the recognition of the RNA virus. In one of three patients with influenza-associated encephalopathy, we detected a novel missense mutation (F303S) in just the TLR3 gene. This was confirmed as a loss-of-function mutant in a dose-dependent manner by NF-kappaB and IFN-beta reporter assays using wild-type and mutant TLR3-transfected HEK293 cells. Our results imply that a mutation of the TLR3 gene could be one of the factors responsible for influenza-associated encephalopathy.
authors.affiliation: Department of Pediatrics, Miyazaki Medical College, University of Miyazaki, 5200 Kihara, Kiyotake-Chou, Miyazaki-Gun, Miyazaki 889-1692, Japan.
authors.forename: Fumio
authors.initials: F
authors.lastname: Hidaka
authors.forename: Susumu
authors.initials: S
authors.lastname: Matsuo
authors.forename: Tatsushi
authors.initials: T
authors.lastname: Muta
authors.forename: Koichiro
authors.initials: K
authors.lastname: Takeshige
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Mizukami
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nunoi
mesh_terms: D002460:Cell Line; D002675:Child, Preschool; D018792:Encephalitis, Viral / Q000209:etiology / Q000235:genetics / Q000276:immunology*; D005260:Female; D017930:Genes, Reporter; D020022:Genetic Predisposition to Disease; D006801:Humans; D009980:Influenza A virus / Q000276:immunology*; D007251:Influenza, Human / Q000150:complications / Q000235:genetics / Q000276:immunology*; D020125:Mutation, Missense; D051196:Toll-Like Receptor 3 / Q000235:genetics*
chemical_list: C495344:TLR3 protein, human; D051196:Toll-Like Receptor 3