Suppression of Japanese encephalitis virus infection by non-steroidal anti-inflammatory drugs.
Japanese encephalitis virus (JEV) infection generates a rapid inflammatory response including peripheral neutrophil leucocytosis and infiltration of neutrophils into extraneural tissue. The level of inflammation correlates well with the clinical outcome in Japanese encephalitis patients. Non-steroidal anti-inflammatory drugs (NSAIDs), used medicinally for their analgesic and anti-inflammatory properties, are being considered for prevention of cardiovascular disease and cancer, as well as for treatment of human immunodeficiency virus infection. Apart from their ability to inhibit prostaglandin synthesis, the mechanisms underlying the beneficial therapeutic effects are largely unknown. We used aspirin, indomethacin and sodium salicylate to study the role of NSAIDs in JEV propagation in vitro. We found that NSAIDs suppressed JEV propagation in neuronal and non-neuronal cells. Blockade of cyclooxygenase activity by NSAIDs caused decreased production of free radicals and prostaglandins. However, these pharmacological alterations did not seem to correlate well with the antiviral effects. When cells were treated with the mitogen-activated protein kinase (MAPK) inhibitors PD 98059 and SB 203580, salicylate lost its antiviral effect. The activation of MAPK by anisomycin mimicked the action of salicylate in suppressing JEV-induced cytotoxicity. The decreased phosphorylation of extracellular signal-regulated kinase (ERK) was induced by JEV infection and the decrease in ERK was reversed by salicylate. Our data suggest that the signalling pathways of MAPK play a role in the antiviral action of salicylate.
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China1.
Chun-Jung
CJ
Chen
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan, Republic of China1.
Shue-Ling
SL
Raung
Institute of Preventive Medicine, National Defence Medical Center, Taipei, Taiwan, Republic of China2.
Ming-Der
MD
Kuo
Institute of Preventive Medicine, National Defence Medical Center, Taipei, Taiwan, Republic of China2.
Yu-Ming
YM
Wang
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D001241:Aspirin / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D002460:Cell Line; D006224:Cricetinae; D003588:Cytopathogenic Effect, Viral / Q000187:drug effects; D004664:Encephalitis Virus, Japanese / Q000187:drug effects* / Q000502:physiology; D007213:Indomethacin / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000037:antagonists & inhibitors; D009474:Neurons; D011453:Prostaglandins / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D012980:Sodium Salicylate / Q000494:pharmacology / Q000627:therapeutic use / Q000633:toxicity; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D011453:Prostaglandins; D017382:Reactive Oxygen Species; D020929:Mitogen-Activated Protein Kinase Kinases; D001241:Aspirin; D012980:Sodium Salicylate; D007213:Indomethacin