Cellular oncogene activation by human cytomegalovirus Lack of correlation with virus infectivity and immediate early gene expression

Istvan Boldogh, S. AbuBakar, D. Millinoff, C. Z. Deng, T. Albrecht

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Abstract

The contribution of expression of human cytomegalovirus (HCMV) immediate early (IE) genes to the rapid and transient increase in cellular (c)-oncogene (fos, jun, myc) transcription following HCMV infection was investigated. A partial temporal overlap was observed between the increases in c-oncogene RNA levels and the increase in either transcripts from HCMV IE genes or the number of cells in which HCMV IE proteins were detected. The increases in c-oncogene RNA levels, however, slightly preceded the increase in the detection of HCMV IE transcripts or proteins. To distinguish between the temporal coincidence and a direct relationship between expression of HCMV IE genes and the increased transcription of c-oncogenes, the number of cells synthesizing HCMV IE proteins was reduced by infecting with virus stock enriched in defective particles. Alternatively, the synthesis of HCMV IE proteins was essentially eliminated by ultra-violet (UV) irradiation of virus stock or by inhibitors of protein synthesis. Virus stocks enriched in defective particles demonstrated a substantially reduced capacity to direct the synthesis of HCMV IE proteins, but were more efficient in activating c-oncogene expression than infectious virus stocks. Elimination of expression of HCMV IE genes by UV-irradiation of virus stock or by inhibiting de novo viral and/or cellular protein synthesis with cycloheximide (100 μg/ml) or anisomycin (100 μg/ml) did not eliminate the HCMV-induced increase in RNA levels of c-oncogenes. These data indicate that activation of these early response cellular genes is independent from de novo expression of HCMV IE proteins, and possibly involves biologically active virion proteins that are related to the induction of a cascade of cellular events associated with the binding of HCMV to its cellular receptor.

Original languageEnglish (US)
Pages (from-to)163-177
Number of pages15
JournalArchives of Virology
Volume118
Issue number3-4
DOIs
StatePublished - Sep 1991

Fingerprint

Immediate-Early Genes
Cytomegalovirus
Oncogenes
Viruses
Gene Expression
RNA
Cell Count
Genetic Transcription
jun Genes
Anisomycin
Proteins
Protein Synthesis Inhibitors
Cytomegalovirus Infections
Cycloheximide
Virion

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Genetics

Cite this

Cellular oncogene activation by human cytomegalovirus Lack of correlation with virus infectivity and immediate early gene expression. / Boldogh, Istvan; AbuBakar, S.; Millinoff, D.; Deng, C. Z.; Albrecht, T.

In: Archives of Virology, Vol. 118, No. 3-4, 09.1991, p. 163-177.

Research output: Contribution to journalArticle

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