title: c-Jun N-terminal kinase activity is required for efficient respiratory syncytial virus production.
abstract: Respiratory syncytial virus (RSV) is a major cause of respiratory infections in infants and the elderly, leading to more deaths than influenza each year worldwide. With no RSV antiviral or efficacious vaccine currently available, improved understanding of the host-RSV interaction is urgently required. Here we examine the contribution to RSV infection of the host stress-regulated c-Jun N-terminal kinase (JNK), for the first time. Peak JNK1/2 phosphoactivation is observed at ∼24 h post-infection, correlating with the time of virus assembly. The release of infectious RSV virions from infected cells was significantly reduced by either JNK1/2 siRNA knockdown or treatment with the JNK-specific inhibitor, JNK-IN-VIII. High resolution microscopy confirmed RSV accumulation in the host cell cytoplasm. The results implicate JNK1/2 as a key host factor for RSV virus production, raising the possibility of agents targeting JNK activity as potential anti-RSV therapeutics.
authors.affiliation: Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Leon
authors.initials: L
authors.lastname: Caly
authors.affiliation: Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia.
authors.forename: Hong-Mei
authors.initials: HM
authors.lastname: Li
authors.affiliation: Cell Signalling Research Laboratories, Bio21 Institute, Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria, 3010, Australia.
authors.forename: Marie A
authors.initials: MA
authors.lastname: Bogoyevitch
authors.affiliation: Nuclear Signalling Laboratory, Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria 3800, Australia. Electronic address: David.Jans@monash.edu.
authors.forename: David A
authors.initials: DA
authors.lastname: Jans
mesh_terms: D000072283:A549 Cells; D004789:Enzyme Activation; D055785:Gene Knockdown Techniques; D054884:Host-Pathogen Interactions / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D006801:Humans; D048055:Mitogen-Activated Protein Kinase 8 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D048056:Mitogen-Activated Protein Kinase 9 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D018113:Respiratory Syncytial Virus, Human / Q000187:drug effects / Q000472:pathogenicity / Q000502:physiology*; D014771:Virion / Q000502:physiology; D019065:Virus Assembly / Q000502:physiology; D057074:Virus Release / Q000502:physiology; D014779:Virus Replication / Q000502:physiology*
chemical_list: D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D048056:Mitogen-Activated Protein Kinase 9; D048055:Mitogen-Activated Protein Kinase 8
keywords: JNK; Respiratory syncytial virus; Viral release; c-Jun N-terminal kinase