%0 Journal Article %A Lin, Ren-Jye %A Liao, Ching-Len %A Lin, Yi-Ling %T Replication-incompetent virions of Japanese encephalitis virus trigger neuronal cell death by oxidative stress in a culture system %D 2004 %J Journal of General Virology, %V 85 %N 2 %P 521-533 %@ 1465-2099 %R https://doi.org/10.1099/vir.0.19496-0 %I Microbiology Society, %X 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-κB), and the addition of anti-oxidants or specific NF-κB 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. %U https://www.microbiologyresearch.org/content/journal/jgv/10.1099/vir.0.19496-0