title: Japanese encephalitis virus disrupts blood-brain barrier and modulates apoptosis proteins in THBMEC cells.
abstract: 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.
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Mazen M Jamil
authors.initials: MMJ
authors.lastname: Al-Obaidi
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Bahadoran
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Lee Sau
authors.initials: LS
authors.lastname: Har
authors.affiliation: Institute of Medical Molecular Biotechnology, Faculty of Medicine, University Technology Mara, Selangor, Malaysia.
authors.forename: Wang Seok
authors.initials: WS
authors.lastname: Mui
authors.affiliation: Department of Molecular Medicine, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Jayakumar
authors.initials: J
authors.lastname: Rajarajeswaran
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia.
authors.forename: Keivan
authors.initials: K
authors.lastname: Zandi
authors.affiliation: Department of Trauma and Emergency Medicine, University Malaya Medical Centre, Kuala Lumpur, Malaysia.
authors.forename: Rishya
authors.initials: R
authors.lastname: Manikam
authors.affiliation: Department of Medical Microbiology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. Electronic address: shamala@um.edu.my.
authors.forename: Shamala Devi
authors.initials: SD
authors.lastname: Sekaran
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics / Q000378:metabolism; D001692:Biological Transport; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000821:virology; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000821:virology; D002460:Cell Line; D002522:Chlorocebus aethiops; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D017097:Electric Impedance; D004664:Encephalitis Virus, Japanese / Q000235:genetics* / Q000472:pathogenicity; D042783:Endothelial Cells / Q000378:metabolism* / Q000821:virology; D053222:Fas Ligand Protein / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D054884:Host-Pathogen Interactions; D006801:Humans; D018971:Insulin-Like Growth Factor Binding Protein 2 / Q000235:genetics / Q000378:metabolism; D008954:Models, Biological; D010539:Permeability; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D014709:Vero Cells; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism; D019014:fas Receptor / Q000235:genetics / Q000378:metabolism
chemical_list: C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; C491901:FAS protein, human; C505661:FASLG protein, human; D053222:Fas Ligand Protein; C577903:IGFBP2 protein, human; D018971:Insulin-Like Growth Factor Binding Protein 2; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D050760:Cyclin-Dependent Kinase Inhibitor p27
keywords: Apoptosis proteins; Blood-brain barrier; Electrical cell-substrate impedance sensing; Japanese encephalitis virus