Premium
Activation of cellular oncogenes by clinical isolates and laboratory strains of human cytomegalovirus
Author(s) -
Boldogh I.,
Abubakar S.,
Fons M. P.,
Deng C. Z.,
Albrecht T.
Publication year - 1991
Publication title -
journal of medical virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.782
H-Index - 121
eISSN - 1096-9071
pISSN - 0146-6615
DOI - 10.1002/jmv.1890340409
Subject(s) - biology , rna , cycloheximide , microbiology and biotechnology , oncogene , human cytomegalovirus , virology , gene expression , transcription (linguistics) , gene , northern blot , cell culture , protein biosynthesis , virus , biochemistry , cell cycle , genetics , linguistics , philosophy
The effect on cellular (c) oncogene RNA levels was investigate 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.