Abstract
This study presents an in vivo 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. In vivo 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.