Retrograde transport of intact poliovirus through the axon via the fast transport system

Retrograde transport of intact poliovirus through the axon via the fast transport system
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DOI:
10.1006/viro.1998.9360
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发表时间:
1998-10-10
期刊:
影响因子:
3.7
通讯作者:
Nomoto, A
Nomoto, A
中科院分区:
医学3区
文献类型:
--
作者:
Ohka, S;Yang, WX;Nomoto, A

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认为肌内接种脊髓灰质炎病毒通过人类、猴和携带人类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。为了深入了解脊髓灰质炎病毒逆行轴突运输的分子机制,导致神经毒力的表达,脊髓灰质炎病毒敏感的ICR-PVRTg 21小鼠系(Tg 21)被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脊髓灰质炎病毒抗原。所有Tg 21小鼠在接种后48小时内,均在接种的四肢出现麻痹症状(初始麻痹),这些小鼠已接种1 × 106 pfu的1型脊髓灰质炎病毒Mahoney株。在接种病毒后不同时间切断坐骨神经的小鼠中观察到这种初始麻痹的出现。结果是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脊髓灰质炎病毒相关材料主要由完整的160 S病毒颗粒组成。与抗PVR单克隆抗体共注射可大大减少160 S颗粒的回收量。这些结果表明,其中一个快速逆行轴突运输系统参与脊髓灰质炎病毒通过坐骨神经传播,IM接种的脊髓灰质炎病毒以PVR依赖性方式作为完整颗粒掺入坐骨神经,就像在人体中一样。(C)北京:科学出版社.
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-relaled 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. (C) 1998 Academic Press.