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

2002; Centers for Disease Control and Prevention; Volume: 8; Issue: 12 Linguagem: Inglês

10.3201/eid0812.020224

1080-6059

Joo-Sung Yang, Mathura P. Ramanathan, Kar Muthumani, Andrew Y. Choo, Sung‐Ha Jin, Qian‐Chun Yu, Daniel S. Hwang, Daniel Choo, Mark D. Lee, Kesen Dang, Waixing Tang, J. Joseph Kim, David B. Weiner,

Viral Infections and Vectors

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.