title: Enhanced production of morbillivirus gene-specific RNAs following induction of the cellular stress response in stable persistent infection.
abstract: Previous in vitro work demonstrated the incorporation of the major inducible 70k heat shock protein (i.e., 72k HSP) into the biologically active light nucleocapsid (L-NC) variant of canine distemper virus (CDV). Here, in vitro induction of the cellular stress response, characterized by elevated cytoplasmic and intranuclear 72k HSP, enhanced L-NC expression in mink lung cells supporting stable persistent infection by raccoon-origin CDV. Increases in L-NC were correlated to increased viral RNA production in cell-free transcriptional assays. The enhanced production of viral transcripts within infected cells following stress response induction was confirmed by slot blot and Northern blot analysis of total cellular RNA and was reflected in increased total viral protein production. Post-shock increases in viral fusion (F) gene transcripts and F protein were associated with dramatic increases in viral cytopathic effect. Modest induction of cell-free infectious viral progeny was also documented. A similar effect of the cellular stress response upon viral protein expression, cytopathic effect, and cell-free infectious progeny release was demonstrated in murine neuroblastoma cells persistently infected with a canine CDV isolate. Alterations of the persistent viral phenotype were independent of the specific mechanism of stress-response induction (i.e., heat or sodium arsenite), supporting the role of the stress response and not a particular stressor in mediating these changes. These results document the ability of the cellular environment to alter persistent viral RNA metabolism, thereby altering the infection phenotype.
authors.affiliation: Department of Veterinary Pathobiology, Ohio State University, Columbus 43210.
authors.forename: M J
authors.initials: MJ
authors.lastname: Oglesbee
authors.forename: H
authors.initials: H
authors.lastname: Kenney
authors.forename: T
authors.initials: T
authors.lastname: Kenney
authors.forename: S
authors.initials: S
authors.lastname: Krakowka
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D002213:Capsid / Q000096:biosynthesis / Q000235:genetics*; D002460:Cell Line; D002474:Cell-Free System; D004279:DNA, Viral / Q000096:biosynthesis / Q000235:genetics; D005814:Genes, Viral; D014644:Genetic Variation; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006358:Hot Temperature; D008168:Lung; D008459:Measles virus / Q000235:genetics* / Q000502:physiology; D008561:Membrane Fusion; D051379:Mice; D008907:Mink; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D014158:Transcription, Genetic; D014407:Tumor Cells, Cultured; D014758:Viral Core Proteins / Q000096:biosynthesis / Q000235:genetics*; D014779:Virus Replication
chemical_list: D004279:DNA, Viral; D006360:Heat-Shock Proteins; D012367:RNA, Viral; D014758:Viral Core Proteins