Melatonin inhibits Japanese encephalitis virus replication and neurotoxicity via calcineurin-autophagy pathways

Author:

Moon Ji-Hong,Hong Jeong-Min,Seol Jae-Won,Park Byung-Yong,Eo Seong Kug,Park Sang-YouelORCID

Abstract

Abstract 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.

Funder

National Research Foundation of Korea

Korea Institute of Planning and Evaluation for Technology in Food, Agriculture and Forestry

Publisher

Springer Science and Business Media LLC

Subject

Cellular and Molecular Neuroscience,General Neuroscience

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