title: Caspase-3 activation and ERK phosphorylation during CVB3 infection of cells: influence of the coxsackievirus and adenovirus receptor and engineered variants.
abstract: Caspase activation and MAP kinase signaling have been implicated in coxsackievirus B3 (CVB3) pathogenesis, and both have been demonstrated late in the virus life cycle. We studied activation of caspase-3, an effector protease of apoptosis, and ERK phosphorylation, indicative of MAPK signaling pathway activation, following CVB3 infection of cells that express the coxsackievirus and adenovirus receptor (CAR) or CAR constructs lacking the cytoplasmic domain, and cells which express no detectable CAR. These experiments showed that a burst of caspase-3 activity preceded lysis of CVB3-infected cells expressing CAR, irrespective of the CAR cytoplasmic domain. In RD cells, which were infected in the absence of detectable CAR, caspase-3 activity increased progressively over 52 h with no apparent burst. ERK phosphorylation also occurred late in the virus life cycle, preceding caspase-3 activation, and occurred in cells expressing full-length CAR but not in RD. These results show that ERK phosphorylation precedes caspase-3 activation, both occur late in the infection, and both are influenced by the presence of CAR.
authors.affiliation: The Picornaviral Research Unit, Discipline of Immunology and Microbiology, Faculty of Medicine and Health Sciences, The University of Newcastle, Newcastle, New South Wales 2300, Australia.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: Cunningham
authors.forename: Nora M
authors.initials: NM
authors.lastname: Chapman
authors.forename: Steven D
authors.initials: SD
authors.lastname: Carson
mesh_terms: D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D002460:Cell Line; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D029822:Enterovirus B, Human / Q000472:pathogenicity*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D011991:Receptors, Virus / Q000378:metabolism*
chemical_list: C568771:CLMP protein, human; D062727:Coxsackie and Adenovirus Receptor-Like Membrane Protein; D011991:Receptors, Virus; C105941:coxsackievirus B receptor; D020928:Mitogen-Activated Protein Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases