Role of reactive oxygen intermediates in Japanese encephalitis virus infection in murine neuroblastoma cells

Infection with Japanese encephalitis virus (JEV), a mosquito-borne, neurotr opic flavivirus, may cause acute encephalitis in humans and induce severe c ytopathic effects in various types of cultured cells. This study attempted to determine whether JEV infection induces free radical generation and whet her oxidative stress contributes to virus-induced cell death in neuroblasto ma cells. A rise in the intracellular level of free radicals indicated by t he 2',7'-dichlorofluorescein fluorescence was observed in N18 cells followi ng JEV infection. Cellular flavon-containing enzymes were involved in JEV-i nduced fluorescent change. Cells were moderately protected from JEV-induced death by diphenyleneiodonium, a flavon-containing enzyme inhibitor, wherea s common antioxidants such as N-acetylcysteine, pyrrolidine dithiocarbamate , Tiron, and Trolox turned out to be ineffective. These results suggest tha t the direct antioxidant action is not helpful in prevention of JEV-induced neuronal cell death. (C) 2001 Elsevier Science Ireland Ltd. All rights res erved.