Bioluminescent imaging and histopathologic characterization of WEEV neuroinvasion in outbred CD-1 mice.
Authors: Phillips Aaron T, Stauft Charles B, Aboellail Tawfik A, Toth Ann M, Jarvis Donald L, Powers Ann M, Olson Ken E
Journal: PloS one
Summary
Western equine encephalitis virus (WEEV) causes severe neurological disease in horses and humans via mosquito transmission, yet the precise mechanisms of how the virus invades the central nervous system remain poorly understood. Phillips and colleagues used a novel approach in outbred mice, engineering a recombinant WEEV strain expressing firefly luciferase to track viral spread in real-time through bioluminescent imaging, combined with detailed histopathological examination guided by imaging data. The research revealed that neuroinvasion occurs primarily through the olfactory tract following intranasal infection, with the olfactory bulb serving as the initial infection site before viral dissemination to other brain regions; the trigeminal nerve provided a secondary route of CNS entry with significant brainstem involvement. Notably, infected neurons vastly outnumbered infected glial cells, and axonal infection patterns indicated viral spread along neuronal pathways rather than cell-to-cell transmission. For equine professionals, these findings underscore the neurotropic nature of WEEV and suggest that early detection of respiratory or nasal involvement could indicate impending neurological involvement; additionally, the bioluminescent imaging methodology offers a quantifiable research platform for evaluating potential antivirals or immunomodulatory treatments against alphaviruses affecting equids.
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Practical Takeaways
- •Understanding that WEEV enters the brain via olfactory and trigeminal nerve routes may inform future prevention and treatment strategies for equine encephalitis cases
- •Bioluminescent imaging methodology could potentially be adapted for monitoring disease progression and therapeutic efficacy in equine research settings
- •This foundational research on WEEV neuroinvasion pathways in mammalian models provides mechanistic insights applicable to understanding equine disease pathogenesis
Key Findings
- •WEEV neuroinvasion occurs primarily through cranial nerves, mainly the olfactory tract, with initial infection of olfactory bulb neurons and subsequent spread to other brain regions
- •Trigeminal nerve serves as an additional route of neuroinvasion with significant viral expression in the brainstem
- •Recombinant WEEV.McM.FLUC virus showed attenuated replication compared to wild-type but produced comparable pathologies
- •Bioluminescent imaging provides quantifiable measurement of alphaviral neural disease progression and enables evaluation of antiviral strategies