Infection with Western equine encephalitis virus causes severe regional glial reactivity and neurodegeneration in the hippocampus with progressive accumulation of amyloid-β.
Publication/Presentation Date
8-28-2026
Abstract
Encephalitic alphaviruses such as Western equine encephalitis virus (WEEV) result in significant morbidity through acute viremia and postencephalitic neurologic dysfunction. Viral neurotropism is linked to chronic glial-mediated neuroinflammation and increased risk for neurodegenerative disorders including Alzheimer disease and Parkinson disease. We previously showed that sublethal WEEV infection induces nigrostriatal gliosis, neuronal loss, and Parkinsonian-like motor deficits in mice. However, the temporal progression of glial activation and neurodegeneration in brain regions relevant to dementia remains unclear. To address this, we performed a longitudinal assessment of hippocampal pathology following intranasal infection with McMillan WEEV. Brain tissue was collected at 1, 2, and 4 weeks postinfection and analyzed using high-content fluorescence imaging, deep learning-based image analysis, and population-level cellular phenotyping. We observed a marked increase in gliosis peaking at 1-week postinfection, coinciding with fibrotic, immune cell-dense lesions that inversely correlated with eosinophilic neuronal density. Automated skeletonization analysis revealed increased astrocyte reactivity and a predominantly bushy microglial morphology at this time point. Heat map densitometry further demonstrated progressive amyloid-β accumulation across all time points. Together, these findings define a dynamic sequence of glial activation, lesion formation, and protein aggregation underlying WEEV-induced hippocampal neurotoxicity.
ISSN
1554-6578
Published In/Presented At
Briggs, A. M., Schuller, A. J., Hager, M. R., Yanouri, O. A., Rocha, S. M., Bantle, C. M., Chatterjee, D., Smeyne, R. J., & Tjalkens, R. B. (2026). Infection with Western equine encephalitis virus causes severe regional glial reactivity and neurodegeneration in the hippocampus with progressive accumulation of amyloid-β. Journal of neuropathology and experimental neurology, nlag097. Advance online publication. https://doi.org/10.1093/jnen/nlag097
Disciplines
Business Administration, Management, and Operations | Health and Medical Administration | Management Sciences and Quantitative Methods
PubMedID
42664399
Department(s)
Administration and Leadership
Document Type
Article