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

BMC Neurosci. 2023 Nov 6;24(1):59. doi: 10.1186/s12868-023-00832-1.

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.

Keywords: Autophagy; Calcineurin; Japanese encephalitis virus; Melatonin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Calcineurin / pharmacology
  • Encephalitis Virus, Japanese* / physiology
  • Encephalitis, Japanese*
  • Humans
  • Melatonin* / pharmacology

Substances

  • Calcineurin
  • Melatonin