Abe S, Ota Y, Koike S, Kurata T, Horie H, Nomura T, Hashizume S, Nomoto A
Japan Poliomyelitis Research Institute, Tokyo, Japan.
Virology. 1995 Feb 1;206(2):1075-83. doi: 10.1006/viro.1995.1030.
The transgenic mice, ICR-PVRTg21, carrying the human poliovirus receptor gene, were intraspinally inoculated with oral poliovirus vaccine viruses and the viruses that had been derived from a vaccine preparation by passagings at 38 degrees. Dose-dependent incidence of paralysis was observed in the transgenic mice inoculated with any of the viruses used. All transgenic mice showing histopathological lesions in the central nervous system appeared to display clinical signs that resembled those observed in human poliomyelitis. These suggest that relative neurovirulence levels of individual virus preparations can be estimated by values of 50% paralysis dose. Indeed, the parameter correlated well with monkey lesion scores of viruses used. Histopathological changes such as degeneration of neurons resemble those displayed by monkeys and were observed in the spinal cord, medulla oblongata, and pons. Thus, the transgenic mice, ICR-PVRTg21, may become a new animal model in place of monkeys for safety testing of oral poliovirus vaccine preparations.
携带人脊髓灰质炎病毒受体基因的转基因小鼠ICR-PVRTg21，经脊髓内接种口服脊髓灰质炎疫苗病毒以及在38℃传代后从疫苗制剂中获得的病毒。在用任何一种所使用的病毒接种的转基因小鼠中观察到了剂量依赖性的麻痹发生率。所有在中枢神经系统出现组织病理学损伤的转基因小鼠似乎都表现出类似于人类脊髓灰质炎所观察到的临床症状。这些表明，可以通过50%麻痹剂量的值来估计单个病毒制剂的相对神经毒力水平。事实上，该参数与所使用病毒的猴病变评分相关性良好。神经元变性等组织病理学变化类似于猴所表现的变化，并在脊髓、延髓和脑桥中观察到。因此，转基因小鼠ICR-PVRTg21可能成为替代猴用于口服脊髓灰质炎疫苗制剂安全性测试的新动物模型。
