Dengue Virus-Induced Reactive Oxygen Species Production in Rat Microglial Cells

• Published in: Japanese Journal of Infectious Diseases Vol. 70; no. 4; pp. 383 - 387
• Main Authors: Suwanprinya, Lattapon, Morales, Noppawan Phumala, Sanvarinda, Pimtip, Dieng, Hamady, Okabayashi, Tamaki, Vargas, Ronald Enrique Morales
• Format: Journal Article
• Language: English
• Published: Japan National Institute of Infectious Diseases, Japanese Journal of Infectious Diseases Editorial Committee 2017; Japan Science and Technology Agency
• Subjects: Activation; Animals; Cell Line; Cell Survival - drug effects; dengue; Dengue fever; Dengue Virus - growth & development; Encephalitis; Encephalitis Virus, Japanese - growth & development; Iron; Iron and steel making; Japanese encephalitis; Microglia; Microglia - metabolism; Microglia - virology; Microglial cells; Multiplicity of infection; Nitric oxide; Nitric Oxide - metabolism; Nitric-oxide synthase; Rats; Reactive oxygen species; Reactive Oxygen Species - metabolism; Reactive Oxygen Species - toxicity; Serotypes; Vector-borne diseases; Viral diseases; Viruses; nitric oxide; dengue; microglia; reactive oxygen species; Japanese encephalitis
• ISSN: 1344-6304; 1884-2836
• DOI: 10.7883/yoken.JJID.2016.236

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.