1887

Abstract

Infection of human embryonic kidney cells with adenovirus type 5 (Ad5) induces aberrations (gaps and breaks) in the cell chromosomes. We have conducted a study utilizing a large number of Ad5 mutants to identify the viral functions that are responsible for the occurrence of cytogenetic damage. The results of our investigation have indicated that expression of the gene products of the Ad5 early region 1A (E1 A) is necessary for the induction of chromosomal aberrations and that other early viral gene products do not appear to contribute to this phenotype. We have also shown that expression of both the major E1 A gene products, the 243 amino acid and the 289 amino acid proteins, is required for induction of damage at wild-type levels, although the 289 amino acid protein appears to retain detectable activity on its own. Lastly, we have observed that deletions in the amino-terminal region of the E1 A proteins and in the transactivating domain of the 289 amino acid protein prevent the occurrence of cytogenetic damage, whereas mutations elsewhere in the proteins do not affect this process.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-71-4-801
1990-04-01
2022-08-17
Loading full text...

Full text loading...

/deliver/fulltext/jgv/71/4/JV0710040801.html?itemId=/content/journal/jgv/10.1099/0022-1317-71-4-801&mimeType=html&fmt=ahah

References

  1. Bellett A. J. D., Waldron-Stevens L. K., Braithwaite A. W., Cheetham B. F. 1982; Spermine and aminoguanidine protect cells from chromosome aberrations induced by adenovirus during the G2 phase of the cell cycle. Chromosoma 84:571–583
    [Google Scholar]
  2. Bellett A. J. D., Li P., David E. T., Mackey E. J., Braithwaite A. W., Cutt J. R. 1985; Control functions of adenovirus transformation region E1 A gene products in rat and human cells. Molecular and Cellular Biology 5:1933–1939
    [Google Scholar]
  3. Bellett A. J. D., Jackson P., David E. T., Bennett E. J., Cronin B. 1989; Functions of the two adenovirus early E1A proteins and their conserved domains in cell cycle alteration, actin reorganization, and gene activation in rat cells. Journal of Virology 63:303–310
    [Google Scholar]
  4. Berk A. J. 1986; Functions of adenovirus E1A. Cancer Surveys 5:367–387
    [Google Scholar]
  5. Bernards R. A., Van Der Eb A. J. 1984; Adenovirus: transformation and oncogenicity. Biochimica et biophysica acta 783:187–204
    [Google Scholar]
  6. Braithwaite A. W., Cheetam B. F., Li P., Parish C. R., Waldron-Stevens L. K., Bellett A. J. D. 1983; Adenovirus-induced alterations in the cell growth cycle: a requirement for expression of E1A but not E1B. Journal of Virology 45:192–199
    [Google Scholar]
  7. Branton P. E., Bayley S. T., Graham F. L. 1985; Transformation by human adenoviruses. Biochimica et biophysica acta 780:67–94
    [Google Scholar]
  8. Chang P. L., Gunby J. L., Tomkins D. J., Mak I., Rosa N. E., Mak S. 1986; Transformation of human cultured fibroblasts with plasmids carrying dominant selection markers and immortalizing potential. Experimental Cell Research 167:407–416
    [Google Scholar]
  9. Chang S. E. 1986; In vitro transformation of human epithelial cells. Biochimica et biophysica acta 823:161–194
    [Google Scholar]
  10. Cheetham B. F., Bellett A. J. D. 1982; A biochemical investigation of the adenovirus-induced G1 to S phase transition: thymidine kinase, ornithine decarboxylase and inhibitors of polyamine biosynthesis. Journal of Cellular Physiology 110:114–122
    [Google Scholar]
  11. Dipaolo J. A. 1983; Relative difficulties in transforming human and animal cells in vitro . Journal of the National Cancer Institute 70:3–8
    [Google Scholar]
  12. Durnam D. M., Smith P. P., Menninger J. C., Mcdougall J. K. 1986; The E1 region of human adenovirus type 12 determines the sites of virally induced chromosomal damage. Cancer Cells 4:349–354
    [Google Scholar]
  13. Egan C., Jelsma T. N., Howe J. A., Bayley S. T., Ferguson B., Branton P. E. 1988; Mapping of the cellular-protein binding sites on the products of the early-region 1A of human adenovirus type 5. Molecular and Cellular Biology 8:3955–3959
    [Google Scholar]
  14. Glenn G. M., Ricciardi R. P. 1985; Adenovirus 5 early region 1A host range mutants hr3, hr4 and hr5 contain point mutations which generate single amino acid substitution. Journal of Virology 56:66–74
    [Google Scholar]
  15. Graham F. L., Smiley J. R., Russell W. C., Nairn R. 1977; Characteristics of a human cell line transformed by DNA from human adenovirus type 5. Journal of General Virology 36:59–72
    [Google Scholar]
  16. Graham F. L., Harrison T., Williams J. 1978; Defective transforming capacity of adenovirus type 5 host-range mutants. Virology 86:10–21
    [Google Scholar]
  17. Haj-Ahmad Y., Graham F. L. 1986; Development of a helper-independent human adenovirus vector and its use in the transfer of the herpes simplex virus thymidine kinase gene. Journal of Virology 57:267–274
    [Google Scholar]
  18. Haley K. P., Overhauser J., Babiss L. E., Ginsberg H. S., Jones N. C. 1984; Transformation properties of type 5 adenovirus mutants that differentially express the E1A gene products. Proceedings of the National Academy of Sciences, U.S.A 81:5734–5738
    [Google Scholar]
  19. Harrison T., Graham F., Williams J. 1977; Host-range mutants of adenovirus type 5 defective for growth in HeLa cells. Virology 77:319–329
    [Google Scholar]
  20. Jelsma T. N., Howe J. A., Evelegh C. M., Cunniff N. F., Skiadopoulos M. H., Floroff M. R., Denman J. E., Bayley S. T. 1988; Use of deletion and point mutants spanning the coding region of the adenovirus 5 E1A gene to define a domain that is essential for transcriptional activation. Virology 163:494–502
    [Google Scholar]
  21. Jelsma T. N., Howe J. A., Mymryk J. S., Evelegh C. M., Cunniff N. A., Bayley S. T. 1989; Sequences in the E1A proteins of human adenovirus 5 required for cell transformation, repression of a transcriptional enhancer, and induction of proliferating cell nuclear antigen. Virology 171:120–130
    [Google Scholar]
  22. Jones N., Shenk T. 1979; Isolation of adenovirus type 5 host range deletion mutants defective for transformation of rat embryo cells. Cell 17:683–689
    [Google Scholar]
  23. Lebeau M. M. 1986; Chromosomal fragile sites and cancer specific rearrangements. Blood 67:849–853
    [Google Scholar]
  24. Liu H. T., Baserga R., Mercer W. E. 1985; Adenovirus type 2 activates cell cycle-dependent genes that are a subset of those activated by serum. Molecular and Cellular Biology 5:2936–2942
    [Google Scholar]
  25. Mcdougall J. K. 1971; Adenovirus-induced chromosome aberrations in human cells. Journal of General Virology 12:43–51
    [Google Scholar]
  26. Montell C., Fisher E. F., Caruthers M. H., Berk A. J. 1982; Resolving the functions of overlapping viral genes by site-specific mutagenesis at a mRNA splice site. Nature 295:380–384
    [Google Scholar]
  27. Moorhead P. S., Saksela E. 1965; The sequence of chromosome aberrations during SV40 transformation of a human diploid cell strain. Hereditas 52:271–284
    [Google Scholar]
  28. Murray J. D., Bellett A. J. D., Braithwaite A. W., Waldron L. K., Taylor I. W. 1982a; Altered cell cycle progression and aberrant mitosis in adenovirus-infected rodent cells. Journal of Cellular Physiology 111:89–96
    [Google Scholar]
  29. Murray J. D., Braithwaite A. D., Taylor I. W., Bellett A. J. D. 1982b; Adenovirus-induced alterations of the cell growth cycle: effects of mutations in early regions E2A and E2B. Journal of Virology 44:1072–1075
    [Google Scholar]
  30. Ricciardi R. P., Jones R. L., Cepko C. L., Sharp P. A., Roberts B. E. 1981; Expression of early adenovirus genes requires a viral encoded polypeptide. Proceedings of the National Academy of Sciences, U.S.A 78:6121–6125
    [Google Scholar]
  31. Rowe D. T., Yee S.-P., Otis J., Graham F. L., Branton P. E. 1983; Characterization of human adenovirus type 5 early region 1A polypeptides using antitumor sera and an antiserum specific for the carboxy terminus. Virology 127:253–271
    [Google Scholar]
  32. Simon M. C., Kitchener C., Kao H.-T., Hickely E., Weber L., Voellmy R., Heintz N., Nevins J. R. 1987; Selective induction of human heat shock gene transcription by the adenovirus El A gene products, including the 12S El A product. Molecular and Cellular Biology 7:2884–2890
    [Google Scholar]
  33. Smith D. H., Ziff E. B. 1988; The amino-terminal region of the adenovirus serotype 5 E1 A protein performs two separate functions when expressed in primary baby rat kidney cells. Molecular and Cellular Biology 8:3882–3890
    [Google Scholar]
  34. Tremblay M. L., Dumont D. J., Branton P. E. 1989; Analysis of phosphorylation sites in the exon 1 region of E1 A proteins of human adenovirus type 5. Virology 169:397–407
    [Google Scholar]
  35. van der Vliet P. C., Sussenbach J. S. 1975; An adenovirus type 5 gene function required for initiation of viral DNA replication. Virology 67:415–426
    [Google Scholar]
  36. Walen K. H. 1987; Chromosome instability in cell lineages of amniocyte clones morphologically transformed by Simian virus 40. Cancer Genetics and Cytogenetics 25:149–159
    [Google Scholar]
  37. Yunis J. J. 1987; Multiple recurrent genomic rearrangements and fragile sites in human cancer. Somatic Cellular and Molecular Genetics 13:397–403
    [Google Scholar]
  38. Zur Hausen H. 1967; Induction of specific chromosomal aberrations by adenovirus type 12 in human embryonic kidney cells. Journal of Virology 1:1174–1185
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-71-4-801
Loading
/content/journal/jgv/10.1099/0022-1317-71-4-801
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error