中枢神经系统的甲病毒感染:进入、传播和神经变性

Phillips AT, Rico AB, Aboellail TA, Olson KE.
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引用次数: 0

摘要

通常与神经侵袭性疾病相关的甲病毒仅限于美洲,包括EEEV、VEEV和WEEV毒株。甲病毒在感染脊椎动物后进入中枢神经系统的过程尚不清楚。据认为,病毒进入中枢神经系统取决于接种途径。嗅感觉神经元在空气传播的病毒攻击后提供进入中枢神经系统的通道,这是公认的。然而,关于外周非嗅觉感染后病毒进入中枢神经系统的知识较少,这似乎依赖于某种形式的血液传播。我们试图通过结合体内/离体生物发光成像和传统组织学检查方法来确定脚垫接种后进入中枢神经系统的精确途径。我们在成像的大脑中发现了一个一致的病毒时空分布模式,其中没有一个涉及嗅球。通过对成像组织进行组织学分析来扩展这些研究,发现WEEV进入中枢神经系统可能发生在血脑屏障自然缺失的中枢神经系统区域。这些区域包括下丘脑、皮质下器官、松果体和后脑区。重要的是,这些结果揭示了一种以前未被认识到的甲病毒进入中枢神经系统的方法。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Alphavirus Infection of the CNS: Entry, Dissemination, and Neurodegeneration

Alphaviruses most often associated with neuroinvasive disease are limited to the Americas and include strains of EEEV, VEEV, and WEEV. The process of alphavirus entry into the CNS of infected vertebrates following challenge is not well-understood. It is thought that virus entry into the CNS depends on the inoculation route. It is well-established that olfactory sensory neurons provide access to the CNS following challenge with airborne virus. However, less knowledge is available regarding virus entry into the CNS following peripheral, non-olfactory infection, which appears to rely on some form of hematogenous spread. We sought to determine the precise route of CNS entry following footpad inoculation by using a combination of in vivo/ex vivo bioluminescence imaging and traditional histological examination methods. We found a consistent pattern in the spatiotemporal distribution of virus among the imaged brains, none of which involved the olfactory bulb. Extending these studies by performing histological analysis on the imaged tissues, led to the finding that CNS entry by WEEV likely occurs in areas of the CNS where the blood-brain barrier is naturally absent. These areas include the hypothalamus, the subfornical organ, the pineal gland, and the area postrema. Importantly, these results reveal a previously unrecognized method of alphavirus entry into the CNS.

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