title: Reovirus infection activates JNK and the JNK-dependent transcription factor c-Jun.
abstract: Viral infection often perturbs host cell signaling pathways including those involving mitogen-activated protein kinases (MAPKs). We now show that reovirus infection results in the selective activation of c-Jun N-terminal kinase (JNK). Reovirus-induced JNK activation is associated with an increase in the phosphorylation of the JNK-dependent transcription factor c-Jun. Reovirus serotype 3 prototype strains Abney (T3A) and Dearing (T3D) induce significantly more JNK activation and c-Jun phosphorylation than does the serotype 1 prototypic strain Lang (T1L). T3D and T3A also induce more apoptosis in infected cells than T1L, and there was a significant correlation between the ability of these viruses to phosphorylate c-Jun and induce apoptosis. However, reovirus-induced apoptosis, but not reovirus-induced c-Jun phosphorylation, is inhibited by blocking TRAIL/receptor binding, suggesting that apoptosis and c-Jun phosphorylation involve parallel rather than identical pathways. Strain-specific differences in JNK activation are determined by the reovirus S1 and M2 gene segments, which encode viral outer capsid proteins (sigma1 and mu1c) involved in receptor binding and host cell membrane penetration. These same gene segments also determine differences in the capacity of reovirus strains to induce apoptosis, and again a significant correlation between the capacity of T1L x T3D reassortant reoviruses to both activate JNK and phosphorylate c-Jun and to induce apoptosis was shown. The extracellular signal-related kinase (ERK) is also activated in a strain-specific manner following reovirus infection. Unlike JNK activation, ERK activation could not be mapped to specific reovirus gene segments, suggesting that ERK activation and JNK activation are triggered by different events during virus-host cell interaction.
authors.affiliation: Departments of Neurology, University of Colorado Health Science Center, Denver, Colorado 80262, USA.
authors.forename: P
authors.initials: P
authors.lastname: Clarke
authors.forename: S M
authors.initials: SM
authors.lastname: Meintzer
authors.forename: C
authors.initials: C
authors.lastname: Widmann
authors.forename: G L
authors.initials: GL
authors.lastname: Johnson
authors.forename: K L
authors.initials: KL
authors.lastname: Tyler
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002213:Capsid / Q000235:genetics; D036022:Capsid Proteins; D002460:Cell Line; D004789:Enzyme Activation; D006388:Hemagglutinins; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology; D012087:Reoviridae / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D014764:Viral Proteins / Q000235:genetics
chemical_list: D036022:Capsid Proteins; D006388:Hemagglutinins; D016755:Proto-Oncogene Proteins c-jun; D018124:Receptors, Tumor Necrosis Factor; D014764:Viral Proteins; C055356:mu1 protein, Reovirus; C031728:sigma 1 protein, reovirus; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases