title: Replication-incompetent virions of Japanese encephalitis virus trigger neuronal cell death by oxidative stress in a culture system.
abstract: It has been shown that replication of the Japanese encephalitis virus (JEV) can trigger infected cells to undergo apoptosis. In the present study, it is further demonstrated that replication-incompetent virions of JEV, obtained by short-wavelength ultraviolet (UV) irradiation, could also induce host-cell death. It was found that UV-inactivated JEV (UV-JEV) caused cell death in neuronal cells such as mouse neuroblastoma N18 and human neuronal NT-2 cells, but not in non-neuronal baby hamster kidney BHK-21 fibroblast or human cervical HeLa cells. Only actively growing, but not growth-arrested, cells were susceptible to the cytotoxic effects of UV-JEV. Killing of UV-JEV-infected N18 cells could be antagonized by co-infection with live, infectious JEV, suggesting that virions of UV-JEV might engage an as-yet-unidentified receptor-mediated death-signalling pathway. Characteristically, mitochondrial alterations were evident in UV-JEV-infected N18 cells, as revealed by electron microscopy and a loss of membrane potential. N18 cells infected by UV-JEV induced generation of reactive oxygen species (ROS) as well as the activation of nuclear factor kappa B (NF-kappaB), and the addition of anti-oxidants or specific NF-kappaB inhibitors to the media greatly reduced the cytotoxicity of UV-JEV. Together, the results presented here suggest that replication-incompetent UV-JEV damages actively growing neuronal cells through a ROS-mediated pathway.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, No. 128, Sec. 2, Yen-Jiou-Yuan Rd, Taipei 11529, Taiwan, Republic of China.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Ren-Jye
authors.initials: RJ
authors.lastname: Lin
authors.affiliation: Department of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan, Republic of China.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Ching-Len
authors.initials: CL
authors.lastname: Liao
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, No. 128, Sec. 2, Yen-Jiou-Yuan Rd, Taipei 11529, Taiwan, Republic of China.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
mesh_terms: D000818:Animals; D016923:Cell Death; D002460:Cell Line; D004664:Encephalitis Virus, Japanese / Q000502:physiology* / Q000528:radiation effects; D008564:Membrane Potentials; D051379:Mice; D008928:Mitochondria / Q000378:metabolism / Q000648:ultrastructure; D016328:NF-kappa B / Q000378:metabolism; D009474:Neurons / Q000378:metabolism / Q000821:virology*; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D014466:Ultraviolet Rays; D014771:Virion / Q000502:physiology / Q000528:radiation effects; D038301:Virus Inactivation
chemical_list: D016328:NF-kappa B; D017382:Reactive Oxygen Species