Abstract

Host Pathogen Interaction in Japanese Encephalitis Virus Infection: From Bench to Bedside

Anirban Basu, Senior Scientist, National Brain Research Center

Minocycline is broadly protective in neurological disease models featuring inflammation and cell death and is being evaluated in clinical trials. Japanese Encephalitis Virus (JEV) is one of the most important causes of viral encephalitis worldwide. There is no specific treatment for JE and no effective anti-viral drugs have been discovered. Studies indicate that JE involves profound neuronal loss as well as secondary inflammation caused due to cell death. Minocycline is a semi synthetic second-generation tetracycline that exerts anti-inflammatory and anti apoptotic effects that are completely separate from its antimicrobial action. Because tetracycline treatment is clinically well tolerated, we investigated whether minocycline protects against experimental model of JE. We show that minocycline at relatively low doses is very effective neuro protective drug against an experimental model of JE even when the administration is started next day following viral inoculation, indicating a clinically relevant therapeutic time window for this tetracycline derivative. Further more, our results also suggested that minocycline rescue 70% of animals even in animals with established infection of JEV. Neuronal apoptosis, microglial activation, active caspase activity, proinflammatory mediators and viral titre were markedly decreased in minocycline-treated JEV infected mice on 9th days post infection. Treatment with minocycline may act directly on brain cells, because neuronal cell line Neuro2a were also salvaged from JEV induced death. Minocycline is a safe drug commonly used for prolonged treatment of infections, rheumatoid arthritis, and acne vulgaris. Based upon our laboratory findings a clinical trial has been initiated at Chhatrapati Shahuji Medical University, Lucknow, in the state of Uttar Pradesh, India.