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Comparison of neuropathogenicity of poliovirus type 3 in transgenic mice bearing the poliovirus receptor gene and cynomolgus monkeys

机译:携带脊髓灰质炎病毒受体基因和食蟹猴的转基因小鼠中3型脊髓灰质炎病毒的神经致病性比较

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To clarify the similarities of poliovirus infection in cynomolgus monkeys and transgenic mice bearing the poliovirus receptor. TgPVR21, we compared the pathological changes of these animals following intraspinal inoculation of two strains of poliovirus type 3 using immunohistochemical detection of the capsid antigen. All of the monkeys inoculated with 10(6) TCID50 viruses showed flaccid paralysis 2 or 3 days post-inoculation (p.i.). TgPVR21 mice showed paralysis starting from 2 to 3 days p.i. Histologically, neurons having pyknotic nuclei and eosinophilic cytoplasm and neuronophagia were characteristically observed in both animals, but central chromatolysis was not observed in infected TgPVR21. The median lesion scores in the monkeys and TgPVR21 were well correlated, though the distribution of poliovirus-infected lesions in the central nervous system was different. In both animals the motor neurons and the brainstem nuclei responsible for flaccid paralysis were infected by the virus, while the cerebral cortex and thalamus were infected in the monkeys but not in TgPVR21. These results confirmed the reliability of neurovirulence tests using TgPVR21 as a substitute for monkeys, in respect to the spinal and brainstem lesions of poliovirus type 3.
机译:为了阐明在食蟹猴和携带脊髓灰质炎病毒受体的转基因小鼠中脊髓灰质炎病毒感染的相似性。 TgPVR21,我们比较了使用衣壳抗原的免疫组织化学检测方法对两株3型脊髓灰质炎病毒进行脊髓内接种后这些动物的病理变化。接种10(6)TCID50病毒的所有猴子在接种后2或3天(p.i.)表现出松弛性麻痹。 TgPVR21小鼠在p.i出现2到3天后出现瘫痪。组织学上,在两只动物中均特征性地观察到具有致死性核和嗜酸性细胞质以及神经噬菌体的神经元,但是在受感染的TgPVR21中未观察到中央层析。尽管脊髓灰质炎病毒感染的病变在中枢神经系统中的分布有所不同,但猴子与TgPVR21的中位病变得分之间存在良好的相关性。在这两只动物中,负责松弛性麻痹的运动神经元和脑干核均被病毒感染,而猴子的大脑皮层和丘脑则被感染,而在TgPVR21中则未被感染。这些结果证实了在3型脊髓灰质炎病毒的脊髓和脑干病变方面,使用TgPVR21替代猴子进行神经毒力测试的可靠性。

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