title: Induction of inflammation by West Nile virus capsid through the caspase-9 apoptotic pathway.
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 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.
authors.affiliation: University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
authors.forename: Joo-Sung
authors.initials: JS
authors.lastname: Yang
authors.forename: Mathura P
authors.initials: MP
authors.lastname: Ramanathan
authors.forename: Karuppiah
authors.initials: K
authors.lastname: Muthumani
authors.forename: Andrew Y
authors.initials: AY
authors.lastname: Choo
authors.forename: Sung-Ha
authors.initials: SH
authors.lastname: Jin
authors.forename: Qian-Chun
authors.initials: QC
authors.lastname: Yu
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Hwang
authors.forename: Daniel K
authors.initials: DK
authors.lastname: Choo
authors.forename: Mark D
authors.initials: MD
authors.lastname: Lee
authors.forename: Kesen
authors.initials: K
authors.lastname: Dang
authors.forename: Waixing
authors.initials: W
authors.lastname: Tang
authors.forename: J Joseph
authors.initials: JJ
authors.lastname: Kim
authors.forename: David B
authors.initials: DB
authors.lastname: Weiner
mesh_terms: D000818:Animals; D017209:Apoptosis; D001921:Brain / Q000821:virology; D036022:Capsid Proteins / Q000235:genetics / Q000502:physiology*; D053453:Caspase 9; D020169:Caspases / Q000502:physiology*; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D014901:West Nile Fever / Q000209:etiology; D014902:West Nile virus / Q000235:genetics / Q000472:pathogenicity*
chemical_list: D036022:Capsid Proteins; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases