Infiltrated monocytes following ZIKV infection drive microglia activation and chronic CNS damage in immunocompetent adult mice 9066

Abstract Description Zika virus (ZIKV) is a neurotropic pathogen linked to neuropathogenesis in adults, causing conditions such as Guillain-Barré syndrome (GBS) and fatal encephalitis. While studies using intracranial injection or infection in immunocompromised mice have shown neuroinflammation and subsequent brain damage, the mechanisms underlying ZIKV-induced neuroinflammation in immunocompetent mice via peripheral infection remain unclear. To investigate this, we utilized a murine model of ZIKV infection through foot-pad injection. Our findings reveal that acute ZIKV infection induces significant neuronal apoptosis and chronic neuroinflammation in the adult brain, persisting up to 28 days post-infection. Notably, ZIKV infection triggers apoptosis in the hippocampus and cortex—key regions involved in memory—and induces early immune cell infiltration. Additionally, microglial activation occurs following infection, with viral proteins detected in the brain. This activation is likely driven by infiltrating monocytes, as inhibiting monocyte recruitment reduced the expression of microglial activation genes. Bulk RNA sequencing of the hippocampus at 28 days post-infection further reveals the activation of inflammatory pathways, underscoring the prolonged neuroinflammatory response in the infected brain. As such, targeting monocyte-induced inflammatory mediators may provide therapeutic intervention. Funding Sources NIH Grant DK122737 to YH Topic Categories Neuroimmunology (NEUR)