Activation of cellular oncogenes by clinical isolates and laboratory strains of human cytomegalovirus.
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.
Boldogh
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I
Department of Microbiology, University of Texas Medical Branch, Galveston 77550.
AbuBakar
S
S
Fons
M P
MP
Deng
C Z
CZ
Albrecht
T
T
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
D000546:Amanitins; D003609:Dactinomycin; D012313:RNA; D003513:Cycloheximide