Two modes of herpesvirus trafficking in neurons: Membrane acquisition directs motion
Two modes of herpesvirus trafficking in neurons: Membrane acquisition directs motion
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DOI：
10.1128/jvi.01441-06
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发表时间：
2006-11-01
影响因子：
5.4
通讯作者：
Smith, Gregory A.
中科院分区：
文献类型：
--
作者：
Antinone, Sarah E.;Smith, Gregory A.
哺乳动物神经系统的甲型疱疹病毒感染依赖于病毒颗粒在轴突中的长距离细胞内运输。病毒颗粒是如何在最初感染后有效地通过轴突运输到感觉神经节，或者在重新激活后返回到周围神经支配部位的，目前尚不清楚。关于衣壳是在没有膜成分的情况下在轴突中运输，还是作为被包裹的病毒粒子运输，轴突运输的机制在一定程度上被相互矛盾的发现所掩盖。通过对活的外周神经元中主动移位的病毒结构成分进行成像，我们证明了疱疹病毒使用两条不同的路径在轴突中移动。进入细胞后，衣壳暴露在胞浆中，导致有效的逆行运输到神经元胞体。相反，后代病毒颗粒在获得病毒被膜蛋白和膜脂后沿顺行方向移动。在这种膜结合状态下，逆行转运被有效地关闭，从而允许将后代病毒颗粒有效地运送到远端轴突。值得注意的是，缺少膜的后代病毒颗粒被错误地定向回细胞体。这些发现表明，胞浆衣壳被运输到神经元细胞体，轴突中的病毒在衣壳被膜包裹后发生外泄。
Alphaherpesvirus infection of the mammalian nervous system is dependent upon the long-distance intracellular transport of viral particles in axons. How viral particles are effectively trafficked in axons to either sensory ganglia following initial infection or back out to peripheral sites of innervation following reactivation remains unknown. The mechanism of axonal transport has, in part, been obscured by contradictory findings regarding whether capsids are transported in axons in the absence of membrane components or as enveloped virions. By imaging actively translocated viral structural components in living peripheral neurons, we demonstrate that herpesviruses use two distinct pathways to move in axons. Following entry into cells, exposure of the capsid to the cytosol resulted in efficient retrograde transport to the neuronal cell body. In contrast, progeny virus particles moved in the anterograde direction following acquisition of virion envelope proteins and membrane lipids. Retrograde transport was effectively shut down in this membrane-bound state, allowing for efficient delivery of progeny viral particles to the distal axon. Notably, progeny viral particles that lacked a membrane were misdirected back to the cell body. These findings show that cytosolic capsids are trafficked to the neuronal cell body and that viral egress in axons occurs after capsids are enshrouded in a membrane envelope.