A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy
A missense mutation of the Toll-like receptor 3 gene in a patient with influenza-associated encephalopathy
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DOI：
10.1016/j.clim.2006.01.005
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发表时间：
2006-05-01
影响因子：
8.6
通讯作者：
Nunoi, H
中科院分区：
文献类型：
--
作者：
Hidaka, F;Matsuo, S;Nunoi, H
Toll样受体（TLR）识别病原体相关的分子模式并介导NF-κ B B的活化和促炎细胞因子的产生，这对于先天免疫系统是至关重要的。TLR 3识别双链RNA和甲型流感病毒。由于流感相关脑病在日本和东亚很常见，其病理机制仍不清楚，我们分析了几个基因，包括TLR和视黄酸诱导基因I，这可能涉及RNA病毒的识别。在3例感染相关脑病患者中，我们仅在TLR 3基因中检测到一种新的错义突变（F303 S）。通过使用野生型和突变型TLR 3转染的HEK 293细胞的NF-κ B和IFN-β报告基因测定，以剂量依赖性方式证实这是一种功能丧失突变体。我们的研究结果表明，TLR 3基因的突变可能是流感相关脑病的因素之一。(c)2006年爱思唯尔公司All rights reserved.
Toll-like receptors (TLRs) recognize pathogen-associated molecular patterns and mediate the activation of NF-kappa B 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 inftuenza-associated encephatopathy, 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-kappa B 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. (c) 2006 Elsevier Inc. All rights reserved.