Al-Obaidi M M Jamil, Bahadoran A, Wang S M, Manikam R, Raju Ch S, Sekaran S D
Acta Virol. 2018;62(1):16-27. doi: 10.4149/av_2018_102.
The blood brain barrier consisting of astrocytes, pericytes and brain microvascular endothelial cells plays a vital role in the pathogenesis of neurotropic viruses by controlling the access of circulating molecules, immune cells or viruses into the central nervous system (CNS). However, this barrier is not impenetrable and neuroviruses have evolved to disrupt and evade it. This review aims to describe the underlying entry mechanisms of several neuroviruses such as (Japanese encephalitis virus (JEV), West Nile virus (WNV), Zika virus (ZIKV), Nipah virus (NiV), Rabies virus (RABV), Herpes simplex virus (HSV) and Human immunodeficiency virus (HIV)) into the CNS through BBB disruption. The mechanisms, through which neurotropic viruses enter the BBB, are being studied and are becoming clearer, however, some aspects still remain unknown. Some of these viruses are able to invade the brain parenchyma by a 'Trojan horse' mechanism, through diapedesis of infected immune cells that either cross the BBB paracellularly or transcellularly. Important mechanisms of BBB disruption associated with paracellular entry of viruses include alterations in expression or phosphorylation of tight junction proteins, disruption of the basal lamina and disruption of the actin cytoskeleton. In the absence of such mechanisms, indirect effects of viruses on the immune system are likely causes of barrier disruption.
由星形胶质细胞、周细胞和脑微血管内皮细胞组成的血脑屏障，通过控制循环分子、免疫细胞或病毒进入中枢神经系统（CNS），在嗜神经病毒的发病机制中起着至关重要的作用。然而，这一屏障并非不可穿透，神经病毒已经进化出破坏和规避它的能力。本综述旨在描述几种神经病毒（如日本脑炎病毒（JEV）、西尼罗河病毒（WNV）、寨卡病毒（ZIKV）、尼帕病毒（NiV）、狂犬病病毒（RABV）、单纯疱疹病毒（HSV）和人类免疫缺陷病毒（HIV））通过破坏血脑屏障进入中枢神经系统的潜在机制。嗜神经病毒进入血脑屏障的机制正在研究中，并且越来越清晰，但仍有一些方面尚不清楚。其中一些病毒能够通过“特洛伊木马”机制，即通过感染的免疫细胞的渗出，以跨细胞或细胞旁的方式穿过血脑屏障，从而侵入脑实质。与病毒细胞旁进入相关的血脑屏障破坏的重要机制包括紧密连接蛋白表达或磷酸化的改变、基膜的破坏和肌动蛋白细胞骨架的破坏。在没有这些机制的情况下，病毒对免疫系统的间接影响可能是屏障破坏的原因。
