Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Letter
  • Published:

Simian virus 40 replication in adenovirus-transformed human cells antagonizes gene expression

Abstract

Simian virus 40 (SV40) replicates efficiently in monkey kidney cells. However, we have now found that SV40-based vectors transfected into most human cells replicate poorly, if at all. In contrast, strong SV40 replication is observed in human embryonic kidney (HEK) cells transformed with the adenovirus early region, but not in untransformed HEK cells. Vector replication in adenovirus-transformed cells is dependent on the presence of the SV40 origin of replication and large-T antigen. However, vigorous replication occurs at levels of large-T antigen that are undetectable by immunofluorescence. These data suggest that the adenovirus oncogenes create a replication-permissive environment to which the SV40 replicon responds. Furthermore, replication and gene expression seem to be antagonistic on our vectors. High levels of large-T antigen are observed only when vector replication is blocked by mutations in the gene for large-T antigen or the origin of replication, or by direct inhibition of DNA polymerase with aphidicolin.

This is a preview of subscription content, access via your institution

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Calos, M. P., Lebkowski, J. S. & Botchan, M. R. Proc. natn. Acad. Sci. U.S.A. 80, 3015–3019 (1983).

    Article  ADS  CAS  Google Scholar 

  2. Lebkowski, J. S., DuBridge, R. B., Antell, E. A., Greisen, K. S. & Calos, M. P. Molec. cell. Biol. 4, 1951–1960 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tooze, J. DNA Tumor Viruses 2nd edn (Cold Spring Harbor Laboratory, New York, 1981).

    Google Scholar 

  4. Lusky, M. & Botchan, M. Nature 293, 79–81 (1981).

    Article  ADS  CAS  PubMed  Google Scholar 

  5. Wigler, M. et al. Cell 16, 777–785 (1979).

    Article  CAS  PubMed  Google Scholar 

  6. Hirt, B. J. molec. Biol. 26, 365–369 (1967).

    Article  CAS  PubMed  Google Scholar 

  7. Bachetti, S. & Graham, F. L. Proc. natn. Acad. Sci. U.S.A. 74, 1590–1594 (1977).

    Article  ADS  Google Scholar 

  8. Major, E. O. & Matsumura, P. Molec. cell. Biol. 4, 379–382 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Imperiale, M. J., Feldman, L. T. & Nevins, J. R. Cell 35, 127–136 (1983).

    Article  CAS  PubMed  Google Scholar 

  10. Green, M. R., Treisman, R. & Maniatis, T. Cell 35, 137–148 (1983).

    Article  CAS  PubMed  Google Scholar 

  11. Treisman, R., Green, M. R. & Maniatis, T. Proc. natn. Acad. Sci. U.S.A. 80, 7428–7432 (1983).

    Article  ADS  CAS  Google Scholar 

  12. Gaynor, R. B., Hillman, D. & Berk, A. J. Proc. natn. Acad. Sci. U.S.A. 81, 1193–1197 (1984).

    Article  ADS  CAS  Google Scholar 

  13. Graham, F. L., Smiley, J., Russell, W. C. & Nairn, R. J. gen. Virol. 36, 59–72 (1977).

    Article  CAS  PubMed  Google Scholar 

  14. Gluzman, Y. Cell 23, 175–182 (1981).

    Article  CAS  PubMed  Google Scholar 

  15. Whittaker, J. L., Byrd, P. J., Grand, R. J. A. & Gallimore, P. H. Molec. cell. Biol. 4, 110–116 (1984).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Gluzman, Y., Frisque, J. & Sambrook, J. Cold Spring Harb. Symp. quant. Biol. 44, 293–300 (1979).

    Article  Google Scholar 

  17. Huberman, J. A. Cell 23, 647–648 (1981).

    Article  CAS  PubMed  Google Scholar 

  18. Yates, J. L., Warren, N. & Sugden, B. Nature 313, 812–815 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  19. Weeks, D. L. & Jones, N. C. Molec. cell. Biol. 3, 1222–1234 (1983).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Alwine, J. C. Molec. cell. Biol. 5, 1034–1042 (1985).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Lewis, E. D. & Manley, J. L. Nature 317, 172–175 (1985).

    Article  ADS  CAS  PubMed  Google Scholar 

  22. Tegtmeyer, P., Schwartz, M., Collins, J. K. & Rundell, K. J. Virol. 16, 168–178 (1975).

    CAS  PubMed  PubMed Central  Google Scholar 

  23. Reed, S. I., Stark, G. R. & Alwine, J. C. Proc. natn. Acad. Sci. U.S.A. 73, 3083–3087 (1976).

    Article  ADS  CAS  Google Scholar 

  24. Tjian, R. Cell 13, 165–179 (1978).

    Article  CAS  PubMed  Google Scholar 

  25. Rio, D., Robbins, A., Myers, R. & Tjian, R. Proc. natn. Acad. Sci. U.S.A. 77, 5706–5710 (1980).

    Article  ADS  CAS  Google Scholar 

  26. Lewton, B. A., DeLucia, A. L. & Tegtmeyer, P. J. Virol. 49, 9–13 (1984).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Harlow, E., Crawford, L. V., Pim, D. C. & Williamson, N. M. J. Virol. 39, 861–869 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Laemmli, U. K. Nature 227, 680–685 (1970).

    Article  ADS  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lebkowski, J., Clancy, S. & Calos, M. Simian virus 40 replication in adenovirus-transformed human cells antagonizes gene expression. Nature 317, 169–171 (1985). https://doi.org/10.1038/317169a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/317169a0

This article is cited by

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing