Acute viral encephalitis impacts dense‐core amyloid plaque pathology and dysregulates myeloid responses to amyloid plaques
Dominic Ibarra Javonillo, Susana Furman, Lucas Le, Kellie Fernandez, Jazmyn Mulford, Vidushi Singla, Roshni Jha, Kate Inman Tsourmas, Nellie E. Kwang, Kim N. Green, Thomas E. LaneAbstract
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
JHMV‐induced encephalitis at 12 days post‐infection resulted in minimal changes to overall Aβ protein, despite increased CD4 + and CD8 + 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.