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Zinc Inhibits BTK Phosphorylation in Macrophages to Ameliorate Encephalitis in Neurotropic Virus-Infected Mice

Xiaochen Sun1, Baokai Zhang1,2, Shengli Zhao2

  • 1School of Medicine, Shanghai University, Shanghai, China.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|June 24, 2026
PubMed

Insights

Zinc supplementation protects against Japanese encephalitis virus (JEV) infection by reducing brain inflammation. This study reveals zinc

Area of Science:

  • Neuroimmunology
  • Virology
  • Nutritional Neuroscience

Background:

  • Zinc is vital for immune function, but its role in neurotropic viral encephalitis is unclear.
  • Japanese encephalitis virus (JEV) causes significant neurological disease.

Purpose of the Study:

  • To investigate the protective role of zinc supplementation against JEV infection in the central nervous system (CNS).
  • To elucidate the underlying mechanisms of zinc's immunomodulatory effects in JEV encephalitis.

Main Methods:

  • A zinc-supplemented (ZnS) dietary intervention was used in a murine model of JEV infection.
  • Macrophage activation, inflammatory markers, and neuronal damage were assessed.
  • Key signaling pathways, including Bruton's tyrosine kinase (BTK) and NF-κB p65, were analyzed.

Main Results:

  • Zinc supplementation significantly protected against JEV infection by suppressing macrophage-mediated inflammation in the CNS.
  • Zinc inhibited the phosphorylation of BTK and NF-κB p65 in macrophages.
  • This led to reduced neuroinflammation and alleviated JEV-induced neuronal damage in the murine brain.

Conclusions:

  • Zinc plays a crucial role in regulating immune responses within the CNS during viral encephalitis.
  • Zinc supplementation represents a potential therapeutic strategy for neurological complications associated with CNS infections like JEV.
Keywords:
JEVbtkencephalitismacrophagezinc

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