title: Activation of cellular oncogenes by clinical isolates and laboratory strains of human cytomegalovirus.
abstract: The effect on cellular (c) oncogene RNA levels was investigated after infection of permissive cells with cell culture adapted strains (AD-169, C-87, Davis) and unadapted clinical isolates (82-1, 84-2, 85-1) of human cytomegalovirus (HCMV). The results indicate that both adapted and unadapted strains of HCMV induce substantial increases in c-oncogene RNA levels for fos, jun, and myc measured by Northern blot hybridization. Elimination of immediate early (IE) protein synthesis between 0 and 3 hrs or reduction of virus infectivity (99.99%) by UV-irradiation did not reduce the increase in c-oncogene RNA levels. Inhibition of viral and cellular protein synthesis by cycloheximide resulted in a high abundance (superinduction) of specific RNAs which hybridized to c-oncogene probes after infection with either adapted or unadapted strains of HCMV. These data suggest that IE viral gene expression is not essential for activation of c-oncogenes. Inhibition of DNA-dependent RNA synthesis by blocking RNA elongation with actinomycin-D or by inhibiting the activity of RNA polymerase II with alpha-amanitin significantly reduced the increase in c-oncogene RNA levels, suggesting that activation of cellular genes by HCMV is controlled at the level of transcription. Activation of c-oncogenes by HCMV may be particularly important because their protein products appear to be involved in initiation and regulation of viral and cellular gene expression.
authors.affiliation: Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
authors.forename: I
authors.initials: I
authors.lastname: Boldogh
authors.forename: S
authors.initials: S
authors.lastname: AbuBakar
authors.forename: M P
authors.initials: MP
authors.lastname: Fons
authors.forename: C Z
authors.initials: CZ
authors.lastname: Deng
authors.forename: T
authors.initials: T
authors.lastname: Albrecht
mesh_terms: D000546:Amanitins / Q000494:pharmacology; D015152:Blotting, Northern; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003587:Cytomegalovirus / Q000235:genetics* / Q000302:isolation & purification / Q000502:physiology / Q000528:radiation effects; D003609:Dactinomycin / Q000494:pharmacology; D005455:Fluorescent Antibody Technique; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D015967:Gene Expression Regulation, Viral / Q000187:drug effects / Q000235:genetics; D006801:Humans; D011519:Proto-Oncogenes / Q000235:genetics*; D012313:RNA / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D000546:Amanitins; D003609:Dactinomycin; D012313:RNA; D003513:Cycloheximide