Abstract
West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs of WNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paralysis or death. We report that the WNV-capsid (Cp) by itself induces rapid nuclear condensation and cell death in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9 activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain or interskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis in vivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viral pathogenesis through induction of the apoptotic cascade.
Highlights
West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens
To attain a better understanding of possible mechanisms of WNV biology, we studied the role of the capsid gene in WNV pathogenesis
Using a Hamilton syringe (Hamilton Co., Reno, NV) with a 30-gauge removable needle, 5 μg of pcWNV-Cp–DJY or pcDNA3.1 DNA, in 5 μL of endotoxin-free water and 0.25% of bupivicaine-HCl in phosphate-buffered saline (PBS) was injected into the frontal cortex with a small animal stereotactic apparatus (Kopf Instruments, Tujunga, CA) as described [10]
Summary
West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. We observed that expression of Cp protein in mouse muscle resulted in apoptosis and inflammation of muscle cells. Direct in vivo expression of WNV-Cp protein in mouse brain resulted in an induction of apoptosis similar to what is observed in natural infection.
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