Pathologic characterization of a murine model of human enterovirus 71 encephalomyelitis

被引:146
作者
Ong, Kien Chai [1 ]
Badmanathan, Munisamy [1 ]
Devi, Shamala
Leong, Kum Loong [2 ]
Cardosa, Mary Jane [3 ]
Wong, Kum Thong [1 ]
机构
[1] Univ Malaya, Dept Pathol, Fac Med, Kuala Lumpur 50603, Malaysia
[2] Univ Malaya, Lab Anim Ctr, Fac Med, Kuala Lumpur 50603, Malaysia
[3] Univ Malaysia Sarawak, Inst Hlth & Community Med, Kota Samarahan, Sarawak, Malaysia
关键词
enterovirus; 71; encephalomyelitis; immunohistochemistry; in situ hybridization; mouse model; viral transmission;
D O I
10.1097/NEN.0b013e31817713e7
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
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.
引用
收藏
页码:532 / 542
页数:11
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