Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis
Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis
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DOI：
10.1097/nen.0b013e31817713e7
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发表时间：
2008-06-01
影响因子：
3.2
通讯作者：
Wong, Kum Thong
中科院分区：
文献类型：
--
作者：
Ong, Kien Chai;Badmanathan, Munisamy;Wong, Kum Thong
我们描述了一种2周龄小鼠的肠道病毒71型脑脊髓炎模型，该模型具有许多与人类中枢神经系统(CNS)疾病相同的特征。小鼠通过口服和非肠道途径感染了一种小鼠适应的病毒株，该病毒株最初来自一例致命的人类病例。小鼠在2-5天后死于感染。原位杂交、免疫组织化学和电子显微镜下可见空泡化的、外观正常的中枢神经系统神经元显示病毒RNA、抗原和病毒粒子；炎症反应轻微。感染神经元以前角、三叉神经运动核团和脑干网状结构最多，红核、小脑外侧核、其他脑神经核团、运动皮质、下丘脑和丘脑较少。其他中枢神经系统区域、背根神经节和自主神经节则幸免于难。肌肉接种感染后24至36小时死亡的小鼠，在同侧腰椎前角细胞和邻近轴突中有病毒RNA和抗原。感染上髓运动神经元、脑干和对侧运动皮质神经元的时间为48~72h。病毒RNA和抗原在骨骼肌和邻近组织中含量丰富，而在其他器官中含量较低。该模型中独特的、典型的病毒分布表明，病毒在骨骼肌感染后通过周围运动神经进入中枢神经系统，并在中枢神经系统内传播涉及运动和其他神经通路。该模型可用于进一步研究发病机制和测试治疗方法。
We describe a model of Enterovirus 71 encephalomyelitis in 2-week-old mice that shares many features with the human central nervous system (CNS) disease. Mice were infected via oral and parenteral routes with a murine-adapted virus strain originally from a fatal human case. The mice succumbed to infection after 2 to 5 days. Vacuolated and normal-appearing CNS neurons showed viral RNA and antigens and virions by in situ hybridization, immunohistochemistry, and electron microscopy; inflammation was minimal. The most numerous infected neurons were in anterior horns, motor trigeminal nuclei, and brainstem reticular formation; fewer neurons in the red nucleus, lateral cerebellar nucleus, other cranial nerve nuclei, motor cortex, hypothalamus, and thalamus were infected. Other CNS regions, dorsal root, and autonomic ganglia were spared. Intramuscular-inoculated mice killed 24 to 36 hours postinfection had viral RNA and antigens in ipsilateral lumbar anterior horn cells and adjacent axons. Upper cord motor neurons, brainstem, and contralateral motor cortex neurons were infected from 48-72 hours. Viral RNA and antigens were abundant in skeletal muscle and adjacent tissues but not in other organs. The distinct, stereotypic viral distribution in this model suggests that the virus enters the CNS via peripheral motor nerves after skeletal muscle infection, and spread within the CNS involves motor and other neural pathways. This model may be useful for further studies on pathogenesis and for testing therapies.