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Title: In-vitro characterization of human brain microvascular endothelial cells infected with West Nile virus to study tight junction integrity 
Author: Lo, Yeung Y
Date: 2008
Abstract: West Nile virus (WNV) is the predominant cause of viral encephalitis in the United States today. Infection of neurons and induction of inflammatory response are cardinal features of fatal WN encephalitis. WNV neuroinvasion has been implicated to occur by hematogenous spread and possibly via the blood-brain barrier (BBB) interface. However, the precise mechanisms of viral entry into the CNS through the brain vascular endothelium, key component of the BBB, are unclear. Cellular and molecular modulations of tight junction proteins (TJP), cell adhesion molecules (CAM) and matrix metalloproteinases (MMP) on brain vascular endothelial cells in response to WNV infection were highly likely to influence transmigration of WNV into the CNS. We hypothesized that WNV could infect and replicate in human brain microvascular endothelial (HBMVE) cells. Further we hypothesized that infection with WNV would lead to modulation in the expressions of TJP, CAM and MMP, thereby leading to enhanced migration of the virus across the BBB. Our results demonstrate that WNV could efficiently replicate in HBMVE cells. In correspondence to the maximal viral replication and virion release on day 2 after infection, WNV claudin-1 transcription and translation were significantly up-regulated. In addition, significant induction of E-selectin and VCAM-1 transcription was detected. VCAM-1 increase was further confirmed at post-translational level. WNV selectively modulated the expressions of CAM and TJP, but none of the MMP examined. These modulations are confirmed to be direct effects of WNV replication as changes in CAM or T JP expressions were not observed in HBMVE cells infected with UV-inactivated WNV. Our in vitro results suggest an active role of brain endothelial cells in WNV neuroinvasion.
Description: Thesis (M.S.)--University of Hawaii at Manoa, 2008. Includes bibliographical references (leaves 72-106). xiv, 106 leaves, bound 29 cm
URI: http://hdl.handle.net/10125/20444
Rights: All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner.

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