title: Stress-activated protein kinases are involved in coxsackievirus B3 viral progeny release.
abstract: Stress-activated protein kinases (SAPKs), consisting of c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase (p38 MAPK), are activated upon various environmental stimuli, including viral infections. Cellular survival and death signaling events following coxsackievirus B3 (CVB3) infection have been studied in relationship to viral replication, but the role of SAPKs has not been scrutinized. In this study, we found that the phosphorylation of JNK1/2 and p38 MAPK was increased during active replication of CVB3 and that their phosphorylation was independent of CVB3-induced caspase activation or production of reactive oxygen species. The roles of these kinases in CVB3 infection were further evaluated using specific inhibitors: SP600125 for JNK1/2 and SB203580 for p38 MAPK. JNK1/2 inhibitors reduced CVB3-induced phosphorylation of activating transcription factor 2, and the p38 MAPK inhibitor reduced CVB3-induced phosphorylation of heat shock protein 27. Although inhibition of these kinases by specific inhibitors did not affect CVB3 viral protein synthesis, inhibition of p38 MAPK but not of JNK1/2 resulted in significant reduction of viral progeny release, suppression of CVB3-induced cell death, and blockage of CVB3-induced caspase-3 activation in infected cells. We conclude that SAPK pathways play critical roles in the life cycle of CVB3, particularly in viral progeny release.
authors.affiliation: Department of Pathology and Laboratory Medicine, The James Hogg iCAPTURE Centre for Cardiovascular and Pulmonary Research, University of British Columbia-St. Paul's Hospital, Vancouver, British Columbia, Canada. hluo@mrl.ubc.ca
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Si
authors.forename: Honglin
authors.initials: H
authors.lastname: Luo
authors.forename: Andrew
authors.initials: A
authors.lastname: Morgan
authors.forename: Jingchun
authors.initials: J
authors.lastname: Zhang
authors.forename: Jerry
authors.initials: J
authors.lastname: Wong
authors.forename: Ji
authors.initials: J
authors.lastname: Yuan
authors.forename: Mitra
authors.initials: M
authors.lastname: Esfandiarei
authors.forename: Guang
authors.initials: G
authors.lastname: Gao
authors.forename: Caroline
authors.initials: C
authors.lastname: Cheung
authors.forename: Bruce M
authors.initials: BM
authors.lastname: McManus
mesh_terms: D002470:Cell Survival; D029822:Enterovirus B, Human / Q000201:enzymology / Q000502:physiology*; D004789:Enzyme Activation; D006367:HeLa Cells; D006801:Humans; D007700:Kinetics; D048055:Mitogen-Activated Protein Kinase 8 / Q000378:metabolism; D048056:Mitogen-Activated Protein Kinase 9 / Q000378:metabolism; D010766:Phosphorylation; D015398:Signal Transduction; D014764:Viral Proteins / Q000096:biosynthesis / Q000235:genetics; D014779:Virus Replication / Q000502:physiology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
chemical_list: D014764:Viral Proteins; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8; D048051:p38 Mitogen-Activated Protein Kinases