Decoding IFN-mediated immunity and cell dynamics in viral encephalitis: Insights from coxsackievirus B3 infection

This study presents an <i>in vivo</i> model of coxsackievirus B3 infection in the brain to examine interferon (IFN) responses and effects on tissue-resident immune cells. Primary cell culture studies revealed that neurons exhibited substantial viral replication with a limited IFN response, whereas microglia, which showed no viral replication, displayed strong immune activation. <i>In vivo</i> analysis captured IFN responses and immune cell dynamics across both acute and chronic inflammation phases. During the acute stage, IFN responses intensified in a dose-dependent manner, with upregulated IFN-stimulated genes (ISGs), increased ISGylation, and microglial activation. Chemokine release coincided with the infiltration of monocytes and T cells in the injured brain. In the chronic phase, viral RNA was undetectable, yet flow cytometry showed persistent T cell presence and low-level microglial activation, indicating ongoing inflammation. This model provides a valuable platform for investigating IFN responses and immune cell interactions in central nervous system (CNS) viral infections and neuroinflammatory conditions.