Induction of Inflammation by West Nile virus Capsid through the Caspase-9 Apoptotic Pathway

摘要

West Nile virus (WNV) is a member of the Flaviviridae family of vector-borne pathogens. Clinical signs ofWNV infection include neurologic symptoms, limb weakness, and encephalitis, which can result in paraly-sis or death. We report that the WNV capsid (Cp) by itself induces rapid nuclear condensation and celldeath in tissue culture. Apoptosis is induced through the mitochondrial pathway resulting in caspase-9activation and downstream caspase-3 activation. Capsid gene delivery into the striatum of mouse brain orinterskeletal muscle resulted in cell death and inflammation, likely through capsid-induced apoptosis invivo. These studies demonstrate that the capsid protein of WNV may be responsible for aspects of viralpathogenesis through induction of the apoptotic cascade