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:

Integration of hepatitis B virus sequences and their expression in a human hepatoma cell

Abstract

Hepatitis derived from hepatitis B virus (HBV) infection is endemic throughout the world, but it is particularly prevalent in Asia and Africa1. In these areas, demographic studies show a strong coincidence between HBV infection (assayed by HBV antigenic markers) and the incidence of primary liver cancer. On these grounds, a causal link between HBV infection and primary hepatocellular cancer has been proposed2–5. Recently, a human hepatoma cell line (PLC/PRF/5; Alexander cells) has been shown to produce hepatitis B surface antigen (HBsAg)6. We show here that the Alexander cell line contains at least six (four complete and two partial) hepatitis B viral genomes integrated into high molecular weight host DNA. An analysis using specific probes to fragments of the HBV genome suggests that integration of the virus in most cases occurs at the nicked cohesive end region of the virus. Expression of viral sequences using Northern blots demonstrates the presence of RNA transcripts specific for the surface antigen sequences of HBV DNA and the absence of detectable transcripts corresponding to the hepatitis B core antigen.

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. Zuckerman, A. J. J. Tox. envir. Hlth 5, 275–280 (1979).

    Article  CAS  Google Scholar 

  2. Zuckerman, A. J. Human Viral Hepatitis, 2nd edn (North-Holland/American Elsevier, Amsterdam, 1975).

    Google Scholar 

  3. Vogel, C. L., Anthony, P. P., Sadikali, F., Barker, L. F. & Peterson, M. R. J. natn. Cancer Inst. 48, 1583–1588 (1972).

    CAS  Google Scholar 

  4. Larouze, B. et al. Lancet ii, 534–538 (1976).

    Article  Google Scholar 

  5. Okuda, K. & Nakashima, T. Prog. Liver Dis. 6, 639–650 (1979).

    CAS  PubMed  Google Scholar 

  6. McNab, G., Alexander, J., Lecatsas, G., Bey, E. & Urbanowicz, J. M. Br. J. Cancer 34, 509–515 (1976).

    Article  Google Scholar 

  7. Alexander, J.J., Beym, E., Geddes, E. & Lecatsas, G. S. Afr. med. J. 50, 2124–2128 (1976).

    CAS  Google Scholar 

  8. Gerin, J. L. & Shih, J. W. K. Viral Hepatitis (eds Vyas, G.N., Cohen, S.N. & Schrmd, R.) 147–153 (Franklin Institute Press, Philadelphia, 1978).

    Google Scholar 

  9. Skelly, J., Copeland, J. A., Howard, C. R. & Zuckerman, A. J. Nature 282, 617–618 (1979).

    Article  ADS  CAS  Google Scholar 

  10. Takahashi, K. et al. J. Immun. 122, 275–279 (1979).

    CAS  Google Scholar 

  11. Dodd, R. Y. et al. in Viral Hepatitis (eds Vyas, G. N., Cohen, S. N. & Schmid, R.) 722 (Franklin Institute Press, Philadelphia, 1978).

    Google Scholar 

  12. Landers, T. A., Greenberg, H. B. & Robinson, W. S. J. Virol. 23, 368–376 (1977).

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Desmyter, J., Ray, M. B., Bradburne, A. F. & Alexander, J. in Viral Hepatitis (eds Vyas, G. N., Cohen, S.N. & Schmid, R.) 459–463 (Franklin Institute Press, Philadelphia, 1978).

    Google Scholar 

  14. Southern, E. M. J. molec. Biol. 98, 503–517 (1975).

    Article  CAS  Google Scholar 

  15. Alwine, J. C., Kemp, D. J. & Stark, G. R. Proc. natn. Acad. Sci. U.S.A. 74, 5350–5354 (1977).

    Article  ADS  CAS  Google Scholar 

  16. Valenzuela, P. et al. Nature 280, 815–819 (1979).

    Article  ADS  CAS  Google Scholar 

  17. Charnay, P., Pourcel, C., Louise, A., Fritsch, A. & Tiollais, P. Proc. natn. Acad. Sci. U.S.A. 76, 2222–2226 (1979).

    Article  ADS  CAS  Google Scholar 

  18. Bailey, J. M. & Davidson, N. Analyt. Biochem. 70, 75–83 (1976).

    Article  CAS  Google Scholar 

  19. Summers, J. et al. J. med. Virol. 2, 207–214 (1978).

    Article  CAS  Google Scholar 

  20. Marion, P. L., Salazar, F. H., Alexander, J. J. & Robinson, W. S. J. Virol. 33, 795–806 (1980).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Tronick, S. R. et al. Proc. natn. Acad. Sci. U.S.A. 76, 6314–6318 (1979).

    Article  ADS  CAS  Google Scholar 

  22. Shank, P. R. et al. Cell 1, 1383–1410 (1978).

    Article  Google Scholar 

  23. Rigby, P. W. J., Dieckman, M., Rhodes, C. & Berg, P. J. molec. Biol. 113, 237–251 (1977).

    Article  CAS  Google Scholar 

  24. Wahl, G. M., Stern, M. & Stark, G. R. Proc. natn. Acad. Sci. U.S.A. 76, 3683–3687 (1979).

    Article  ADS  CAS  Google Scholar 

  25. Chirgwin, J. M., Przybyla, A. E., MacDonald, R. J. & Rutter, W. J. Biochemistry 18, 5294–5299 (1979).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Edman, J., Gray, P., Valenzuela, P. et al. Integration of hepatitis B virus sequences and their expression in a human hepatoma cell. Nature 286, 535–538 (1980). https://doi.org/10.1038/286535a0

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/286535a0

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