title: The West Nile virus capsid protein blocks apoptosis through a phosphatidylinositol 3-kinase-dependent mechanism.
abstract: West Nile virus (WNV) is a mosquito-transmitted pathogen that can cause serious disease in humans. Our laboratories are focused on understanding how interactions between WNV proteins and host cells contribute to virus replication and pathogenesis. WNV replication is relatively slow, and on the basis of earlier studies, the virus appears to activate survival pathways that delay host cell death during virus replication. The WNV capsid is the first viral protein produced in infected cells; however, its role in virus assembly is not required until after replication of the genomic RNA. Accordingly, from a temporal perspective, it is perfectly suited to block host cell apoptosis during virus replication. In the present study, we provide evidence that the WNV capsid protein blocks apoptosis through a phosphatidylinositol (PI) 3-kinase-dependent pathway. Specifically, expression of this protein in the absence of other viral proteins increases the levels of phosphorylated Akt, a prosurvival kinase that blocks apoptosis through multiple mechanisms. Treatment of cells with the PI 3-kinase inhibitor LY294002 abrogates the protective effects of the WNV capsid protein.
authors.affiliation: Departments of Cell Biology, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Matt D
authors.initials: MD
authors.lastname: Urbanowski
authors.forename: Tom C
authors.initials: TC
authors.lastname: Hobman
mesh_terms: D000818:Animals; D017209:Apoptosis; D036022:Capsid Proteins / Q000378:metabolism*; D002460:Cell Line; D002867:Chromones / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000378:metabolism; D054884:Host-Pathogen Interactions; D006801:Humans; D009025:Morpholines / Q000378:metabolism; D058539:Phosphatidylinositol 3-Kinase / Q000378:metabolism*; D000081082:Phosphoinositide-3 Kinase Inhibitors; D014902:West Nile virus / Q000276:immunology / Q000472:pathogenicity*
chemical_list: D036022:Capsid Proteins; D002867:Chromones; D004791:Enzyme Inhibitors; D009025:Morpholines; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D058539:Phosphatidylinositol 3-Kinase