Replication-incompetent virions of Japanese encephalitis virus trigger neuronal cell death by oxidative stress in a culture system.
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.
Lin
Ren-Jye
RJ
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.
Liao
Ching-Len
CL
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.
Lin
Yi-Ling
YL
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.
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
D016328:NF-kappa B; D017382:Reactive Oxygen Species