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

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Summary

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.

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References

  1. AbuBakar S, Boldogh I, Albrecht T (1990) Stimulation of arachidonic acid metabolism: an early event in human cytomegalovirus infection. Arch Virol 3: 255–266

    Google Scholar 

  2. AbuBakar S, Boldogh I, Albrecht T (1990) Human cytomegalovirus stimulates arachidonic acid metabolism through pathways that are affected by inhibitors of phospholipase A2 and protein kinase C. Biochem Biophys Res Com 166: 953–959

    Google Scholar 

  3. Adlish JD, Lahijani RS, St Jeor SC (1990) Identification of a putative cell receptor for human cytomegalovirus. Virology 176: 337–345

    Google Scholar 

  4. Albrecht T, Weller TH (1980) Heterogeneous morphologic features of plaques induced by five strains of human cytomegalovirus. Am J Clin Pathol 73: 648–654

    Google Scholar 

  5. Albrecht T, Boldogh I, Fons M, AbuBakar S, Deng CZ (1990) Cell activation signals and pathogenesis of human cytomegalovirus. Intervirology 31: 68–75

    Google Scholar 

  6. Albrecht T, Boldogh I, Fons M, Lee CH, AbuBakar S, Russell JM, Au WW (1989) Cell-activation responses to cytomegalovirus infection: relationship to the phasing of CMV replication and to the induction of cellular damage. Subcell Biochem 15: 157–202

    Google Scholar 

  7. Albrecht T, St Jeor SC, Funk FD, Rapp F (1974) Multiplicity reactivation of human cytomegalovirus inactivated by ultra-violet light. Int J Radiat Biol 26: 445–454

    Google Scholar 

  8. Barry PA, Pratt-Love E, Peterlin BM, Luciw PA (1990) Cytomegalovirus activates transcription directed by the long terminal repeat of human immunodeficiency virus type 1. J Virol 64: 2932–2940

    Google Scholar 

  9. Ben-Porat T, DeMarchi JM, Kaplan SA (1974) Characterization of defective interfering particles present in a population of pseudorabies virions. Virology 60: 29–37

    Google Scholar 

  10. Boldogh I, AbuBakar S, Albrecht T (1990) Activation of proto-oncogenes: an immediate early event in human cytomegalovirus infection. Science 247: 561–564

    Google Scholar 

  11. Boldogh I, AbuBakar S, Deng CZ, Albrecht T (1991) Transcriptional activation of cellular oncogenes, fos, jun, and myc by human cytomegalovirus. J Virol 65 (in press)

  12. Cherrington JM, Mocarski ES (1989) Human cytomegalovirus IE1 transactivates the alpha promoter enhancer via an 18-base-pair repeat element. J Virol 63: 1435–1440

    Google Scholar 

  13. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal Biochem 162: 156–159

    Google Scholar 

  14. Davis MG, Kenney SC, Kamine J, Pagano JS, Huang ES (1987) Immediate-early gene region of human cytomegalovirus transactivates the promoter of human immunodeficiency virus. Proc Natl Acad Sci USA 84: 8642–8646

    Google Scholar 

  15. DeMarchi JM, Kaplan AS (1977) The role of defective cytomegalovirus particles in the induction of host cell DNA synthesis. Virology 82: 93–99

    Google Scholar 

  16. Frenkel N, Jacob RJ, Honess RW, Hayward GS, Locker H, Roizman B (1975) Anatomy of herpes simplex virus DNA. III. Characterization of defective DNA molecules and biological properties of virus populations containing them. J Virol 16: 153–167

    Google Scholar 

  17. Frenkel N, Locker H, Batterson W, Hayward GS, Roizman B (1976) Anatomy of herpes simplex virus DNA. VI. Defective DNA originates from the S component. J Virol 20: 527–531

    Google Scholar 

  18. Gibson W (1981) Immediate-early proteins of human cytomegalovirus strains AD169, Davis, and Towne differ in electrophoretic mobility. Virology 112: 350–354

    Google Scholar 

  19. Gough NN (1988) Rapid and quantitative preparation of cytoplasmic RNA from a small number of cells. Anal Biochem 173: 93–95

    Google Scholar 

  20. Greenberg ME, Hermanowski AL, Ziff EB (1986) Effect of protein synthesis inhibitors on growth factor activation ofc-fos, c-myc, andactin gene transcription. Mol Cell Biol 6: 1050–1057

    Google Scholar 

  21. Hagemeier C, Sissons JGP, Sinclair JH (1990) The binding of nuclear factors to the cAMP responsive element is associated with major immediate-early gene mediated transactivation ofc-fos upon infection with human cytomegalovirus. In: Abstracts of papers presented at 15th International Herpesvirus Workshop, August 2–8, 1990, Washington, DC, p 77

  22. Huang AS (1973) Defective interfering viruses. Annu Rev Microbiol 27: 101–117

    Google Scholar 

  23. Jahn G, Knust E, Schmolla H, Sarre T, Nelson JA, McDougall JK, Fleckenstein B (1984) Predominant immediate-early transcripts of human cytomegalovirus AD169. J Virol 49: 363–370

    Google Scholar 

  24. Keay S, Merigan TC, Rasmussen L (1989) Identification of cell surface receptors for the 86-kilodalton glycoprotein of human cytomegalovirus. Proc Natl Acad Sci USA 86: 10100–10103

    Google Scholar 

  25. Kouzarides T, Bankier AT, Satchwell ScC, Preddy E, Barell BG (1988) An immediate early gene of human cytomegalovirus encodes a potential membrane glycoprotein. Virology 165: 151–164

    Google Scholar 

  26. Lafemina RL, Pizzorno MC, Moska JD, Hayward GS (1989) Expression of the acidic nuclear immediate-early protein (IE1) of human cytomegalovirus in stable cell lines and its preferential association with metaphase chromosomes. Virology 1742: 584–600

    Google Scholar 

  27. Landschulz WH, Johnson PF, McKnight SL (1988) The leucine zipper: a hypothetical structure common to a new class of DNA binding proteins. Science 240: 1759–1764

    Google Scholar 

  28. Li JKK, Dasker B, Kowalik T (1987) Rapid alkaline blot-transfer of viral dsRNA. Anal Biochem 163: 210–214

    Google Scholar 

  29. Mar EC, Patel PC, Huang ES (1981) Human cytomegalovirus associated DNA polymerase and protein kinase activities. J Gen Virol 57: 149–156

    Google Scholar 

  30. Michelson-Fiske S, Horodniceanu F, Guillon J-C (1977) Immediate early antigens in human cytomegalovirus infected cells. Nature 270: 615–617

    Google Scholar 

  31. Nelson JA, Gnann Jr JW, Ghazal P (1990) Regulation and tissue-specific expression of human cytomegalovirus. Curr Top Microbiol Immunol 154: 75–100

    Google Scholar 

  32. Pizzorno MC, O'Hare P, Sha L, LaFemina RL, Hayward GS (1988) Trans-activation and autoregulation of gene expression by immediate early region 2 gene products of human cytomegalovirus. J Virol 62: 1167–1179

    Google Scholar 

  33. Reedman BM, Klein G (1973) Cellular localization of an Epstein-Barr virus (EBV)-associated complement-fixing antigen in producer and non-producer lymphoblastoid cell lines. J Natl Cancer Inst 11: 499–520

    Google Scholar 

  34. Roby C, Gibson W (1986) Characterization of phosphoproteins and protein kinase activity of virions, noninfectious enveloped particles, and dense bodies of human cytomegalovirus. J Virol 59: 714–727

    Google Scholar 

  35. Sambucetti LC, Cherrington JM, Wilkinson GWG, Mocarski ES (1989) NF-kB activation of the cytomegalovirus enhancer is mediated by a viral transactivator and by T cell stimulation. EMBO J 8: 4251–4258

    Google Scholar 

  36. Santomenna LD, Colberg-Poley AM (1990) Stimulation of cellular HSP70 expression by human cytomegalovirus immediate early gene products. In: Abstracts of papers presented at the 15th International Herpesvirus Workshop, August 2–8, 1990, Washington, DC, p 86

  37. Siess W (1989) Molecular mechanism of platelet activation. Physiol Rev 69: 58–178

    Google Scholar 

  38. Somogyi T, Michelson S, Masse M-J (1990) Genomic localization of a human cytomegalovirus protein kinase activity (PK68). Virology 174: 276–285

    Google Scholar 

  39. Spector DH, Klucher KM, Rabert DK, Wright DA (1990) Human cytomegalovirus early gene expression. Curr Top Microbiol Immunol 154: 21–45

    Google Scholar 

  40. Stamminger T, Fleckenstein B (1990) Immediate-early transcription regulation of human cytomegalovirus. Curr Top Microbiol Immunol 154: 3–19

    Google Scholar 

  41. Stinski MF (1983) Molecular biology of cytomegaloviruses. In: Roizman B (ed) The herpes viruses, vol 2. Plenum, New York, pp 67–113

    Google Scholar 

  42. Stinski MF, Mocarski ES, Thomson DR (1979) DNA of human cytomegalovirus: size heterogeneity and defectiveness resulting from serial undiluted passage. J Virol 31: 231–239

    Google Scholar 

  43. Stinski MF, Roehr TJ (1985) Activation of the major immediate early gene of human cytomegalovirus by cis-acting elements in the promoter-regulatory sequence and by virus-specific trans-acting components. J Virol 55: 431–441

    Google Scholar 

  44. Taylor HP, Cooper NR (1989) Human cytomegalovirus binding to fibroblasts is receptor mediated. J Virol 63: 3991–3998

    Google Scholar 

  45. Tenney DJ, Colberg-Poley AM (1990) RNA analysis and isolation of cDNAs derived from the human cytomegalovirus immediate-early region at 0.24 map units. Intervirology 31: 203–214

    Google Scholar 

  46. Tevethia MJ, Spector DJ, Leisure KM, Stinski MF (1987) Participation of two human cytomegalovirus immediate early gene regions in transcriptional activation of adenovirus promoters. Virology 161: 276–285

    Google Scholar 

  47. Valyi-Nagy T, Bandi Z, Boldogh I, Albrecht T (1988) Hydrolysis of inositol lipids: an early signal of human cytomegalovirus infection. Arch Virol 101: 199–207

    Google Scholar 

  48. Yao F, Courtney RJ (1989) A major transcriptional regulatory protein (ICP4) of herpes simplex type 1 is associated with purified virion. J Virol 63: 3338–3344

    Google Scholar 

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  1. I. Boldogh

    Present address: Department of Microbiology, Medical University of Debrecen, Debrecen, Hungary

Authors and Affiliations

  1. Department of Microbiology, The University of Texas Medical Branch, Galveston, Texas, USA

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

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  2. S. AbuBakar
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  3. D. Millinoff
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  4. C. Z. Deng
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  5. T. Albrecht
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Boldogh, I., AbuBakar, S., Millinoff, D. et al. Cellular oncogene activation by human cytomegalovirus Lack of correlation with virus infectivity and immediate early gene expression. Archives of Virology 118, 163–177 (1991). https://doi.org/10.1007/BF01314027

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  • DOI: https://doi.org/10.1007/BF01314027

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