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

Zinc is an essential micronutrient with well-characterized immunomodulatory properties and has been widely investigated in viral infectious diseases, yet its specific functional role in neurotropic viral encephalitis remains poorly elucidated. In this study, we demonstrate that a zinc-supplemented (ZnS) dietary intervention confers protection against Japanese encephalitis virus (JEV) infection by suppressing macrophage-mediated inflammatory pathology in the central nervous system (CNS). Besides, zinc inhibited the phosphorylation of Bruton's tyrosine kinase (BTK) and NF-κB p65 in macrophages, thereby effectively curbing excessive neuroinflammation and alleviating JEV-induced neuronal damage in the murine brain. Our findings have identified a previously unrecognized mechanism by which zinc regulates immune responses in the central nervous system, and suggest zinc supplementation as a potential intervention for neurological complications arising from central nervous system infections.