Measles virus spread between neurons requires cell contact but not CD46 expression, syncytium formation, or extracellular virus production
Measles virus spread between neurons requires cell contact but not CD46 expression, syncytium formation, or extracellular virus production
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DOI：
10.1128/jvi.74.4.1908-1918.2000
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发表时间：
2000-02-01
影响因子：
5.4
通讯作者：
Rall, GF
中科院分区：
文献类型：
--
作者：
Lawrence, DMP;Patterson, CE;Rall, GF
亚急性硬化性全脑炎 (SSPE) 患者与大脑中持续性麻疹病毒 (MV) 感染有关，尽管存在病毒 RNA 和蛋白质，但几乎无法回收感染性病毒。基于对 SSPE 患者脑组织的研究以及我们对感染 MV 的 NSE-CD46(+) 小鼠（神经元上表达麻疹受体 CD46）的研究，多项证据表明病毒在中枢神经系统中的传播机制与在非神经元细胞中的传播机制不同。为了检查病毒传播的这种替代机制以及正常传播机制丧失的基础，在转基因小鼠的原代 CD46(+) 神经元和分化的人类 NT2 神经元中评估了 MV Edmonston 的感染和传播。正如预期的那样，与成纤维细胞之间的传播不同，神经元之间的病毒传播发生在没有合胞体形成且细胞外病毒最少的情况下。电子显微镜分析表明，尽管核衣壳存在于细胞质中并在细胞膜上排列，但病毒出芽并未从神经元表面发生。我们观察到许多核衣壳存在于神经元过程中并在突触前神经元膜上排列的例子。 CD46(+)和CD46(-)神经元的共培养表明神经元之间的MV传播需要细胞接触而不是CD46表达。总的来说，这些结果表明，神经元环境在病毒组装水平上阻止了神经元之间 MV 传播的正常机制，但允许另一种不依赖于 CD46 的病毒传播机制（可能通过突触）。
In patients with subacute sclerosing panencephalitis (SSPE), which is associated,vith persistent measles virus (MV) infection in the brain, little infectious virus can be recovered despite the presence of viral RNA and protein. Based on studies of brain tissue from SSPE patients and our work with MV-infected NSE-CD46(+) mice, which express the measles receptor CD46 on neurons, several lines of evidence suggest that the mechanism of viral spread in the central nervous system differs from that in nonneuronal cells. To examine this alternate mechanism of viral spread, as well as the basis for the loss of normal transmission mechanisms, infection and spread of MV Edmonston was evaluated in primary CD46(+) neurons from transgenic mice and differentiated human NT2 neurons. As expected, unlike that between fibroblasts, viral spread between neurons occurred in the absence of syncytium formation and with minimal extracellular virus. Electron microscopy analysis showed that viral budding did not occur from the neuronal surface, although nucleocapsids were present in the cytoplasm and aligned at the cell membrane. We observed many examples of nucleocapsids present in the neuronal processes and aligned at presynaptic neuronal membranes. Cocultures of CD46(+) and CD46(-)neurons showed that cell contact but not CD46 expression is required for MV spread between neurons. Collectively, these results suggest that the neuronal environment prevents the normal mechanisms of MV spread between neurons at the level of viral assembly but allows an alternate, CD46-independent mechanism of viral transmission, possibly through the synapse.