Acute viral encephalitis impacts dense‐core amyloid plaque pathology and dysregulates myeloid responses to amyloid plaques

INTRODUCTION: Recent epidemiological datasets have associated viral encephalitis exposure (i.e., viral-induced neuroinflammation) with increased risk of Alzheimer's disease (AD) and dementia, highlighting the need to uncover how it may impact AD neuropathology. METHODS: Aged 5xFAD and wild-type (WT) mice were infected with the John Howard Mueller strain of murine hepatitis virus (JHMV), a neurotropic strain of murine coronavirus to comprehensively determine how coronavirus-induced encephalitis may induce molecular and cellular changes that impact beta-amyloid (Aβ) neuropathology. RESULTS: T-cell infiltration and Lgals3/MAC2-expressing macrophages surrounding more compact Aβ plaques in the brain. Spatial transcriptomic imaging and pathway analysis of differentially expressed genes (DEGs) within myeloid cells demonstrate down-regulated disease-associated (DAM) pathways involving Aβ clearance, response to lipids, and macrophage activation within infected 5xFAD brains. CONCLUSIONS: JHMV encephalitis induces dysregulated gene expression and myeloid cell responses to Aβ plaque burden in 5xFAD mouse brains.