A conserved alpha-herpesvirus protein necessary for axonal localization of viral membrane proteins.

A conserved alpha-herpesvirus protein necessary for axonal localization of viral membrane proteins.
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DOI:
10.1083/jcb.200011146
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发表时间:
2001-08-20
期刊:
The Journal of cell biology
影响因子:
--
通讯作者:
Enquist LW
Enquist LW
中科院分区:
其他
文献类型:
--
作者:
Tomishima MJ;Enquist LW

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伪狂犬病毒是一种α-疱疹病毒,能够感染神经系统,并在不同宿主的突触连接神经元之间传播。至少有三种病毒膜蛋白(gE, gI和Us9)是感染在受感染的啮齿动物中从突触前神经元向突触后神经元传播(顺行传播)所必需的。为了了解这些蛋白如何影响神经元之间的顺行传播,我们分析了野生型或突变型病毒感染培养大鼠交感神经元后病毒蛋白的亚细胞定位。在Us9-null突变体感染而非gE-null突变体感染后,只有一部分病毒结构蛋白进入轴突。令人惊讶的是,在轴突中检测到衣壳蛋白和被膜蛋白,而没有检测到病毒膜蛋白。Us9错义突变体在啮齿动物神经系统中的传播与轴突定位的病毒膜蛋白的数量相关。我们得出结论,Us9膜蛋白控制多种病毒膜蛋白的轴突定位,但不控制衣壳或被膜蛋白的轴突定位。这些数据支持一个模型,即病毒粒子亚组件而不是完整的病毒粒子在轴突中运输。我们的结果为病毒粒子组装和退出神经元的过程提供了新的见解,导致疱疹病毒在神经系统中的定向传播。
Pseudorabies virus, an α-herpesvirus, is capable of infecting the nervous system and spreading between synaptically connected neurons in diverse hosts. At least three viral membrane proteins (gE, gI, and Us9) are necessary for the spread of infection from presynaptic to postsynaptic neurons (anterograde spread) in infected rodents. To understand how these proteins effect anterograde spread between neurons, we analyzed the subcellular localization of viral proteins after infection of cultured rat sympathetic neurons with wild-type or mutant viruses. After Us9-null mutant infections but not gE-null mutant infections, only a subset of the viral structural proteins had entered axons. Surprisingly, capsid and tegument proteins but not viral membrane proteins were detected in axons. The spread of Us9 missense mutants in the rodent nervous system correlated with the amount of viral membrane proteins localized to axons. We conclude that the Us9 membrane protein controls axonal localization of diverse viral membrane proteins but not that of capsid or tegument proteins. The data support a model where virion subassemblies but not complete virions are transported in the axon. Our results provide new insight into the process of virion assembly and exit from neurons that leads to directional spread of herpesviruses in the nervous system.
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