title: Dengue Virus-Induced Reactive Oxygen Species Production in Rat Microglial Cells.
abstract: Encephalitis has been described worldwide as a severe complication in patients infected by dengue virus. Reactive oxygen species (ROS) production is a key mechanism involved in the neuronal damage caused by viral encephalitis. In the present study, the capability of dengue virus serotypes 2 (DENV2) and DENV4 to induce ROS production was investigated in a rat microglial cell line, HAPI cells. The cells were infected with DENV2 and DENV4 at a multiplicity of infection of 0.1 for a 2-h adsorption period. Japanese encephalitis virus (JEV) was used as the reference. DENV2- and DENV4-induced microglial activation and significantly increased ROS production corresponded to decreased cell viability. The activity of DENV4 was significantly higher than the activities of DENV2 and JEV at 48 and 72 h post infection. DENV4 partly induced ROS production via an iron-induced Fenton reaction, as demonstrated by the treatment with an iron chelator, deferiprone. Despite the induction of increased inducible nitric oxide synthase expression and nitric oxide (NO) production by JEV, DENV2, and DENV4 did not induce NO production, suggesting the activation of different pathways in response to infections by different viruses. In conclusion, DENV2 and DENV4 have the capability to induce ROS production and activate microglia, which have been reported as the key components of neuronal damage.
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University.
authors.forename: Lattapon
authors.initials: L
authors.lastname: Suwanprinya
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University.
authors.forename: Noppawan Phumala
authors.initials: NP
authors.lastname: Morales
authors.affiliation: Department of Pharmacology, Faculty of Science, Mahidol University.
authors.forename: Pimtip
authors.initials: P
authors.lastname: Sanvarinda
authors.affiliation: Institute of Biodiversity and Environmental Conservation, Universiti Malaysia Sarawak.
authors.forename: Hamady
authors.initials: H
authors.lastname: Dieng
authors.affiliation: Mahidol-Osaka Center for Infectious Diseases (MOCID), Mahidol University.|Department of Virology, Research Institute for Microbial Diseases, Osaka University.
authors.forename: Tamaki
authors.initials: T
authors.lastname: Okabayashi
authors.affiliation: Department of Medical Entomology, Faculty of Tropical Medicine, Mahidol University.
authors.forename: Ronald Enrique
authors.initials: RE
authors.lastname: Morales Vargas
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003716:Dengue Virus / Q000254:growth & development*; D004664:Encephalitis Virus, Japanese / Q000254:growth & development; D017628:Microglia / Q000378:metabolism* / Q000821:virology*; D009569:Nitric Oxide / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism* / Q000633:toxicity
chemical_list: D017382:Reactive Oxygen Species; D009569:Nitric Oxide
keywords: Japanese encephalitis; dengue; microglia; nitric oxide; reactive oxygen species