OBJECTIVE Herpes simplex virus infection through the neuronal route is the most well-studied mode of viral encephalitis that can persists in a human host for a lifetime. However, the involvement of other possible infection mechanisms by the virus remains underexplored. Therefore, this study aims to determine the temporal effects and mechanisms by which the virus breaches the human brain micro-vascular endothelial cells of the blood-brain barrier. METHOD An electrical cell-substrate impedance-sensing tool was utilized to study the real-time cell-cell barrier or morphological changes in response to the virus infection. RESULTS Herpes simplex virus, regardless of type (i.e., 1 or 2), reduced the cell-cell barrier resistance almost immediately after virus addition to endothelial cells, with negligible involvement of cell-matrix adhesion changes. There is no exclusivity in the infection ability of endothelial cells. From 30 h after HSV infection, there was an increase in cell membrane capacitance with a subsequent loss of cell-matrix adhesion capability, indicating a viability loss of the infected endothelial cells. CONCLUSION This study shows for the first time that destruction of human brain micro-vascular endothelial cells as an in vitro model of the blood-brain barrier could be an alternative invasion mechanism during herpes simplex virus infection.

中文翻译：

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单纯疱疹病毒感染过程中转染的人脑微血管内皮细胞完整性的丧失。

目的通过神经元途径感染单纯疱疹病毒是研究最深入的病毒性脑炎模式，可在人类宿主中持续一生。但是，该病毒是否还涉及其他可能的感染机制。因此，本研究旨在确定病毒破坏血脑屏障的人脑微血管内皮细胞的时间效应和机制。方法利用电-细胞-基底阻抗传感工具研究实时细​​胞-细胞屏障或病毒感染后形态变化。结果无论类型（即1或2），单纯疱疹病毒几乎都会在病毒添加到内皮细胞后立即降低细胞对细胞屏障的抵抗力，而细胞-基质粘附变化的影响可忽略不计。内皮细胞的感染能力没有排他性。从HSV感染后30小时开始，细胞膜电容增加，随后细胞基质粘附能力下降，表明感染的内皮细胞丧失活力。结论这项研究首次表明，破坏人脑微血管内皮细胞作为血脑屏障的体外模型可能是单纯疱疹病毒感染期间的另一种入侵机制。