Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis.
Human TRAF3 adaptor molecule deficiency leads to impaired Toll-like receptor 3 response and susceptibility to herpes simplex encephalitis.
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DOI：
10.1016/j.immuni.2010.08.014
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发表时间：
2010-09-24
期刊：
影响因子：
32.4
通讯作者：
Casanova JL
中科院分区：
文献类型：
--
作者：
Pérez de Diego R;Sancho-Shimizu V;Lorenzo L;Puel A;Plancoulaine S;Picard C;Herman M;Cardon A;Durandy A;Bustamante J;Vallabhapurapu S;Bravo J;Warnatz K;Chaix Y;Cascarrigny F;Lebon P;Rozenberg F;Karin M;Tardieu M;Al-Muhsen S;Jouanguy E;Zhang SY;Abel L;Casanova JL
肿瘤坏死因子受体相关因子3(TRAF3)位于多种受体下游，可诱导干扰素-α、干扰素-α和干扰素-β的产生，其中包括Toll样受体3(Toll样受体3)，而单纯疱疹病毒1型脑炎患者缺乏这种受体。缺乏TRAF3的小鼠在新生期死亡，阻碍了对TRAF3在体内免疫反应和宿主防御中的作用的直接研究。在这里，我们报告了一例有儿童期HSE病史的年轻人的常染色体显性遗传性人类TRAF3缺乏症。TRAF3突变等位基因是一种表达缺失、功能丧失、显性阴性的表型，在刺激肿瘤坏死因子受体和诱导产生干扰素的受体时，该突变等位基因与TRAF3依赖的反应受损有关，但不是取消的。TRAF3缺乏与一种临床表型局限于HSE有关，这是由于依赖TLR3的干扰素诱导功能受损所致。因此，TLR3介导的中枢神经系统对HSV-1原发感染的免疫依赖于TRAF3。常染色体显性遗传性TRAF3缺乏症是单纯疱疹病毒性脑炎的一种遗传病因。R118W TRAF3等位基因为功能缺失、表达缺失、显性阴性。人类TRAF3缺乏会损害TLR3依赖的抗病毒干扰素的诱导。
Tumor necrosis factor (TNF) receptor-associated factor 3 (TRAF3) functions downstream of multiple receptors that induce interferon-α (IFN-α), IFN–β and IFN-λ production, including Toll-like receptor 3 (TLR3), which is deficient in some patients with herpes simplex virus-1 encephalitis (HSE). Mice lacking TRAF3 die in the neonatal period, preventing direct investigation of the role of TRAF3 in immune responses and host defenses in vivo. Here we reported the autosomal dominant, human TRAF3 deficiency in a young adult with a history of HSE in childhood. The TRAF3 mutant allele was a loss-of-expression, loss-of-function, dominant-negative phenotype, and was associated with impaired, but not abolished TRAF3-dependent responses upon stimulation of both TNF receptors and receptors that induce IFN production. TRAF3 deficiency was associated with a clinical phenotype limited to HSE resulting from the impairment of TLR3-dependent induction of IFN. Thus, TLR3-mediated immunity against primary infection by HSV-1 in the central nervous system is critically dependent on TRAF3. Autosomal dominant TRAF3 deficiency is a genetic etiology of herpes simplex encephalitis. R118W TRAF3 allele is loss-of-function, loss-of-expression, and dominant-negative. Human TRAF3 deficiency impairs the TLR3-dependent induction of anti-viral interferons.
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影响因子：
30.8
作者：
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通讯作者：
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影响因子：
15.3
作者：
Filipe-Santos, Orchidee;Bustamante, Jacinta;Haverkamp, Margje H;Vinolo, Emilie;Ku, Cheng-Lung;Puel, Anne;Frucht, David M;Christel, Karin;von Bernuth, Horst;Jouanguy, Emmanuelle;Feinberg, Jacqueline;Durandy, Anne;Senechal, Brigitte;Chapgier, Ariane;Vogt, Guillaume;de Beaucoudrey, Ludovic;Fieschi, Claire;Picard, Capucine;Garfa, Meriem;Chemli, Jalel;Bejaoui, Mohamed;Tsolia, Maria N;Kutukculer, Necil;Plebani, Alessandro;Notarangelo, Luigi;Bodemer, Christine;Geissmann, Frederic;Israel, Alain;Veron, Michel;Knackstedt, Maike;Barbouche, Ridha;Abel, Laurent;Magdorf, Klaus;Gendrel, Dominique;Agou, Fabrice;Holland, Steven M;Casanova, Jean-Laurent
通讯作者：
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