Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis
Axonal transport mediates West Nile virus entry into the central nervous system and induces acute flaccid paralysis
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DOI：
10.1073/pnas.0705837104
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发表时间：
2007-10-23
影响因子：
11.1
通讯作者：
Diamond, Michael S.
中科院分区：
文献类型：
--
作者：
Samuel, Melanie A.;Wang, Hong;Diamond, Michael S.
西尼罗病毒（WNV）已成为流行性病毒性脑炎和弛缓性肢体麻痹的重要病因，但其进入中枢神经系统的机制仍不确定。我们使用区隔化的神经元培养来证明西尼罗河病毒通过轴突运输在逆行和顺行方向上传播。西尼罗河病毒的跨神经元传播需要轴突释放病毒颗粒，并通过添加治疗性中和抗体来阻断。为了验证轴突运输在体内的生理意义，我们直接用西尼罗河病毒接种仓鼠坐骨神经。腹膜内感染导致后肢同侧麻痹，而非注射部位对侧麻痹。肢体麻痹可以通过手术切除坐骨神经或用治疗性中和抗体治疗来阻断。总的来说，这些研究证实西尼罗河病毒在神经元中进行双向传播，轴突转运促进病毒进入中枢神经系统和急性肢体瘫痪。此外，抗体治疗直接抑制西尼罗河病毒感染的跨神经元传播，防止体内瘫痪的发展。
West Nile virus (WNV) has emerged as a significant cause of epidemic viral encephalitis and flaccid limb paralysis, yet the mechanism by which it enters the CNS remains uncertain. We used compartmentalized neuron cultures to demonstrate that WNV spreads in both retrograde and anterogracle directions via axonal transport. Transneuronal spread of WNV required axonal release of viral particles and was blocked by addition of a therapeutic neutralizing antibody. To test the physiologic significance of axonal transport in vivo, we directly inoculated the sciatic nerve of hamsters with WNV. Intrasciatic infection resulted in paralysis of the hind limb ipsilateral but not contralateral to the injection site. Limb paralysis was blocked either by surgical transection of the sciatic nerve or treatment with the therapeutic neutralizing antibody. Collectively, these studies establish that WNV undergoes bidirectional spread in neurons and that axonal transport promotes viral entry into the CNS and acute limb paralysis. Moreover, antibody therapeutics directly inhibit transneuronal spread of WNV infection and prevent the development of paralysis in vivo.