Amanatidou Virginia, Sourvinos George, Apostolakis Stavros, Tsilimigaki Amalia, Spandidos Demetrios A
Laboratory of Clinical Virology, Medical School, University of Crete, Greece.
Pediatr Infect Dis J. 2006 May;25(5):410-4. doi: 10.1097/01.inf.0000214998.16248.b7.
Recent data suggest that immunologic response during respiratory syncytial virus (RSV) infection is partially modified through interaction of viral G glycoprotein with the host's chemokine receptor, CX3CR1. We hypothesized that two nonsynonymous, single-nucleotide polymorphisms of the CX3CR1 gene (CX3CR1-V249I and CX3CR1-T280M) that disrupt the affinity of CX3CR1 for its natural ligand (fractalkine) could also affect the G glycoprotein-CX3CR1 pathway.
To test the hypothesis, DNA samples were obtained from 82 children hospitalized for RSV bronchiolitis in a 1-year period. One hundred twenty sex-matched healthy adults, without a history of severe lower respiratory tract infections, formed the control group.
Epidemiologic data showed an increase in the RSV infection rate during the late winter season, with a peak rate in early spring. Genotyping revealed predominance of the 280M-containing genotypes (M/M or T/M) in cases compared with controls (37.8% versus 20.8%, respectively; odds ratio, 2.03; 95% confidence interval, 1.1-3.9; P = 0.025), demonstrating an association between the common CX3CR1-T280M variations and increased risk of severe RSV bronchiolitis.
Our findings support the hypothesis of the pivotal role of the G glycoprotein CX3CR1 pathway in the pathogenesis of RSV bronchiolitis and propose CX3CR1 as a potential therapeutic target.
近期数据表明，呼吸道合胞病毒（RSV）感染期间的免疫反应可通过病毒G糖蛋白与宿主趋化因子受体CX3CR1的相互作用而部分改变。我们推测，CX3CR1基因的两个非同义单核苷酸多态性（CX3CR1-V249I和CX3CR1-T280M）破坏了CX3CR1与其天然配体（ fractalkine）的亲和力，也可能影响G糖蛋白-CX3CR1途径。
为验证该假设，在1年时间内从82名因RSV细支气管炎住院的儿童中获取DNA样本。120名无严重下呼吸道感染病史、性别匹配的健康成年人组成对照组。
流行病学数据显示，冬末RSV感染率上升，在早春达到峰值。基因分型显示，与对照组相比，病例组中含280M的基因型（M/M或T/M）占优势（分别为37.8%和20.8%；优势比为2.03；95%置信区间为1.1-3.9；P = 0.025），表明常见的CX3CR1-T280M变异与严重RSV细支气管炎风险增加之间存在关联。
我们的研究结果支持G糖蛋白CX3CR1途径在RSV细支气管炎发病机制中起关键作用的假设，并提出CX3CR1作为潜在治疗靶点。
