Induction of inflammation by West Nile virus capsid through the caspase-9 apoptotic pathway.
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.
Yang
Joo-Sung
JS
University of Pennsylvania, School of Medicine, Philadelphia 19104, USA.
Ramanathan
Mathura P
MP
Muthumani
Karuppiah
K
Choo
Andrew Y
AY
Jin
Sung-Ha
SH
Yu
Qian-Chun
QC
Hwang
Daniel S
DS
Choo
Daniel K
DK
Lee
Mark D
MD
Dang
Kesen
K
Tang
Waixing
W
Kim
J Joseph
JJ
Weiner
David B
DB
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*
D036022:Capsid Proteins; C506434:Casp9 protein, mouse; D053453:Caspase 9; D020169:Caspases