Ohka S, Yang W X, Terada E, Iwasaki K, Nomoto A
Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo, 108-8639, Japan.
Virology. 1998 Oct 10;250(1):67-75. doi: 10.1006/viro.1998.9360.
Intramuscularly inoculated poliovirus is thought to spread to the central nervous system through neural pathways in humans, monkeys, and the transgenic (Tg) mice carrying the human poliovirus receptor (PVR) gene. To gain insight into molecular mechanisms for the retrograde axonal transport of poliovirus, resulting in the expression of neurovirulence, a poliovirus-sensitive ICR-PVRTg21 mouse line (Tg21) was used as an animal model for poliomyelitis. We detected poliovirus antigens in axons of the sciatic nerve. All of the Tg21 mice, which had been inoculated into the calves with 1 x 10(6) pfu of the Mahoney strain of type 1 poliovirus, showed symptoms of paralysis in the inoculated limbs (initial paralysis) within 48 h after the inoculation. The appearance of this initial paralysis was observed in mice whose sciatic nerves were transected at various times after virus inoculation. The results were indicators of the velocity of poliovirus transportation through the sciatic nerves under analysis. Poliovirus-related materials recovered from the sciatic nerve were mainly composed of intact 160S virion particles. The amount of 160S particle recovered was greatly reduced by coinjection with anti-PVR monoclonal antibody. These results suggest that one of the fast retrograde axonal transport systems is involved in poliovirus dissemination through the sciatic nerve and that IM-inoculated poliovirus is incorporated into the sciatic nerve as intact particles in a PVR-dependent manner, as it is in humans.
肌肉注射接种的脊髓灰质炎病毒被认为可通过人类、猴子以及携带人脊髓灰质炎病毒受体（PVR）基因的转基因（Tg）小鼠的神经通路传播至中枢神经系统。为深入了解脊髓灰质炎病毒逆行轴突运输导致神经毒力表达的分子机制，将对脊髓灰质炎病毒敏感的ICR-PVRTg21小鼠品系（Tg21）用作脊髓灰质炎的动物模型。我们在坐骨神经的轴突中检测到了脊髓灰质炎病毒抗原。所有用1×10(6) 蚀斑形成单位（pfu）的1型脊髓灰质炎病毒Mahoney株接种到小腿的Tg21小鼠，在接种后48小时内接种肢体均出现麻痹症状（初始麻痹）。在病毒接种后不同时间切断坐骨神经的小鼠中观察到了这种初始麻痹的出现。这些结果是所分析的脊髓灰质炎病毒通过坐骨神经运输速度的指标。从坐骨神经中回收的与脊髓灰质炎病毒相关的物质主要由完整的160S病毒粒子组成。与抗PVR单克隆抗体共注射后，回收的160S粒子数量大幅减少。这些结果表明，快速逆行轴突运输系统之一参与了脊髓灰质炎病毒通过坐骨神经的传播，并且肌肉注射接种的脊髓灰质炎病毒与在人类中一样，以PVR依赖的方式作为完整粒子被纳入坐骨神经。
