Gene expression analysis in the thalamus and cerebrum of horses experimentally infected with West Nile virus.
Authors: Bourgeois Melissa A, Denslow Nancy D, Seino Kathy S, Barber David S, Long Maureen T
Journal: PloS one
Summary
# Editorial Summary: West Nile Virus and Central Nervous System Gene Expression in Horses Researchers used advanced sequencing techniques to map which genes activate in the horse brain and spinal cord during West Nile virus infection, comparing vaccinated horses, naive horses exposed to the virus, and unexposed controls. Their custom microarray identified over 41,000 sequences from brain tissue, with 90% sequence identity to human genes, allowing robust pathway analysis of immune and neurological responses. Exposure to WNV triggered significant changes in 9,020 genes across the thalamus and cerebrum, with survival correlating strongly to heightened immune gene expression—particularly increased pentraxin 3 (a key acute-phase protein) and suppressor of cytokine signaling 3. Critically, WNV-exposed horses showed decreased expression in glutamate and dopamine signalling pathways, suggesting that excitotoxic neuronal damage and dopamine depletion underpin the neurological clinical signs observed in affected animals. These findings provide a molecular framework for understanding WNV neuropathology in horses and may guide future therapeutic targets aimed at modulating neuroimmune responses during acute infection or supporting neurological recovery in surviving animals.
Read the full abstract on PubMed
Practical Takeaways
- •WNV infection triggers significant changes in neurological signaling pathways that correlate with clinical neurological signs; monitoring dopamine and glutamate-related symptoms may help identify affected horses
- •Pentraxin 3 and suppressor of cytokine signaling 3 expression levels may serve as biomarkers to assess immune response and predict survival outcomes in WNV cases
- •Vaccination appears to alter the gene expression profile compared to naive exposure, suggesting different immune pathway activation that warrants further investigation for vaccine efficacy assessment
Key Findings
- •Gene expression profiles differed significantly between WNV-exposed and control horses, with 9,020 sequences showing virus exposure-related changes
- •Pentraxin 3 showed the highest expression increase in all WNV-exposed horses, indicating activation of innate immunity
- •Decreased glutamate and dopamine signaling pathway expression in WNV-infected horses suggests possible glutamate excitotoxicity and dopamine-related neurological dysfunction
- •High sequence homology (90.17% average identity) exists between equine and human transcriptomes, with 31,473 equine sequences aligning to human sequences