C4亚型人肠道病毒71型的小鼠肌肉适应株对小鼠具有致死毒力

目的 人肠道病毒71型( EV71)感染婴幼儿可导致手足口病,偶尔伴随有严重的并发症.建立EV71的小鼠模型是深入研究病毒感染的致病机制、进行疫苗和药物评价的基础.方法将EV71的临床分离株在小鼠骨骼肌中进行系列传代,得到了小鼠的肌肉适应株MP10.使用MP10经腹腔注射感染10日龄ICR小鼠,对感染小鼠的症状、病毒复制和病理进行了监测.结果 与临床分离株相比,MP10对人横纹肌瘤细胞(rhabdomyosarcoma cell,RD细胞)的感染力提高,并且对小鼠的毒力增强,MP10感染10日龄小鼠可导致其瘫痪和死亡.病毒主要在骨骼肌中复制,并引发大面积的坏死性肌炎,同时神经组织未观察到病变.病理分析发现:感染小鼠体内与呼吸运动相关的肌肉均发生严重的坏死性肌炎,推测此类肌肉的坏死会影响小鼠的呼吸功能,从而成为导致小鼠死亡的因素之一.结论 建立了C4亚型EV71毒株感染10日龄ICR小鼠的模型,该模型可作为研究EV71感染的致病机制、以及疫苗和药物评价的工具.

A Mouse-muscle-adapted Human Enterovirus 71 Strain of C4 Subgenotype Causes Lethal Symptoms in Mice

Objective To establish the mouse model for application in the study of pathogenesis of EV71 infection and evaluation of vaccines or drugs.Methods A mouse-adapted strain MP10 was generated by a series of passages of the parental EV71 strain in the skeletal muscle of mice.And then the symptoms,virus replication and pathological changes of tissues of infected-mice were monitored.Results Compared to the parental strain,MP10 showed enhanced infectivity in RD cells and virulence in mice,and MP10 infection caused paralysis and death in 10-day-old mice.Skeletal muscle was the main site for virus replication and showed extensive necrotizing myositis,whereas no lesions were observed in neurological tissues.The muscles associated with respirometric activity showed severe necrosis,which might have caused the infected mice to experience difficulty in breath and was thought to be the cause of death.Conclusion The 10-day-old mouse model for lethal EV71 infection was established and it would be useful for vaccine and drug evaluation.