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  1. Lee SH, Atiya N, Wang SM, Manikam R, Raju CS, Sekaran SD
    Intervirology, 2018;61(4):193-203.
    PMID: 30541013 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.

    Matched MeSH terms: Blood-Brain Barrier/virology*
  2. Ismail AA, Mahboob T, Samudi Raju C, Sekaran SD
    Trop Biomed, 2019 Dec 01;36(4):888-897.
    PMID: 33597462
    Zika virus (ZIKV) is a mosquito-borne Flaviviruses. ZIKV is known to cause birth defect in pregnant women, especially microcephaly in the fetus. Hence, more study is required to understand the infection of Zika virus towards human brain microvascular endothelial cells (MECs). In this study, brain MECs were infected with ZIKV at MOI of 1 and 5 in vitro. The changes in barrier function and membrane permeability of ZIKV-infected brain MECs were determined using electric cell-substrate impedance sensing (ECIS) system followed by gene expression of ZIKV-infected brain MECs at 24 hours post infection using one-color gene expression microarray. The ECIS results demonstrated that ZIKV infection enhances vascular leakage by increasing cell membrane permeability via alteration of brain MECs barrier function. This was further supported by high expression of proinflammatory cytokine genes (lnc-IL6-2, TNFAIP1 and TNFAIP6), adhesion molecules (CERCAM and ESAM) and growth factor (FIGF). Overall, findings of this study revealed that ZIKV infection could alter the barrier function of brain MECs by altering adhesion molecules and inflammatory response.
    Matched MeSH terms: Blood-Brain Barrier/virology*
  3. Al-Obaidi MMJ, Bahadoran A, Har LS, Mui WS, Rajarajeswaran J, Zandi K, et al.
    Virus Res, 2017 04 02;233:17-28.
    PMID: 28279803 DOI: 10.1016/j.virusres.2017.02.012
    Japanese encephalitis (JE) is a neurotropic flavivirus that causes inflammation in central nervous system (CNS), neuronal death and also compromises the structural and functional integrity of the blood-brain barrier (BBB). The aim of this study was to evaluate the BBB disruption and apoptotic process in Japanese encephalitis virus (JEV)-infected transfected human brain microvascular endothelial cells (THBMECs). THBMECs were overlaid by JEV with different MOIs (0.5, 1.0, 5.0 and 10.0) and monitored by electrical cell-substrate impedance sensing (ECIS) in a real-time manner in order to observe the barrier function of THBMECs. Additionally, the level of 43 apoptotic proteins was quantified in the virally infected cells with different MOIs at 24h post infection. Infection of THBMEC with JEV induced an acute reduction in transendothelial electrical resistance (TEER) after viral infection. Also, significant up-regulation of Bax, BID, Fas and Fasl and down-regulation of IGFBP-2, BID, p27 and p53 were observed in JEV infected THBMECs with 0.5 and 10 MOIs compared to uninfected cells. Hence, the permeability of THBMECs is compromised during the JEV infection. In addition high viral load of the virus has the potential to subvert the host cell apoptosis to optimize the course of viral infection through deactivation of pro-apoptotic proteins.
    Matched MeSH terms: Blood-Brain Barrier/virology
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