Loss of Transfected Human Brain Micro-Vascular Endothelial Cell Integrity during Herpes Simplex Virus Infection

• Main Authors: Atiya, N. (Author), Lee, S.H (Author), Manikam, R. (Author), Raju, C.S (Author), Sekaran, S.D (Author), Wang, S.M (Author)
• Format: Article
• Language: English
• Published: S. Karger AG 2018
• Subjects: Article; biological model; blood brain barrier; Blood brain barrier; Blood-Brain Barrier; Capacitance; cell adhesion; cell loss; cell structure; cell survival; Cell Survival; controlled study; Electric Impedance; Electrical cell-substrate impedance sensing; Endothelial Cells; endothelium cell; extracellular matrix; growth, development and aging; herpes simplex; Herpes simplex virus; Herpes simplex virus 2; human; Human alphaherpesvirus 1; human cell; Humans; impedance; in vitro study; Models, Biological; nonhuman; physiology; priority journal; Resistance; Simplexvirus; transfected cell line; vascular endothelial cell; Viral encephalitis; virology; virus encephalitis
• Online Access: View Fulltext in Publisher; View in Scopus
• ISBN: 03005526 (ISSN)
• DOI: 10.1159/000495180

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. © 2018 S. Karger AG, Basel. Copyright: All rights reserved.