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Melatonin inhibits Japanese encephalitis virus replication and neurotoxicity via calcineurin-autophagy pathways
Ji-Hong Moon1, Jeong-Min Hong1, Jae-Won Seol1
1Biosafety Research Institute, College of Veterinary Medicine, Jeonbuk National University, Gobong ro, Iksan, Jeonbuk, 54596, South Korea.
Background:
Japanese encephalitis virus (JEV) is a mosquito-borne flavivirus that has no specific treatment except for supportive medical care. JEV is a neurotropic virus that affects the nervous system and triggers inflammation in the brain.
Methods:
Melatonin is used as a sleep-inducing agent in neurophysiology and may serve as a protective agent against neurological and neurodegenerative diseases. Herein, we investigated the effects of melatonin and the critical roles of the serine/threonine protein phosphatase calcineurin during JEV infection in SK-N-SH neuroblastoma cells.
Results:
Melatonin treatment decreased JEV replication and JEV-mediated neurotoxicity. Calcineurin activity was increased by JEV infection and inhibited by melatonin treatment. Through calcineurin regulation, melatonin decreased the JEV-mediated neuroinflammatory response and attenuated JEV-induced autophagy.
Conclusions:
Calcineurin inactivation has a protective effect in JEV-infected neuronal cells, and melatonin is a novel resource for the development of anti-JEV agents.
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