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Identification of the gene responsible for human T-cell leukaemia virus transcriptional regulation

Nature volume 318, pages 571–574 (1985)Cite this article

Abstract

Human T-cell leukaemia viruses (HTLVs) have genomic organization distinct from that of other replication-competent retroviruses, possessing four genes, gag, pol, env and χ. The unique fourth gene, χ (also referred to as lor), is located between env and the 3′ long terminal repeat (LTR), encoding a protein of relative molecular mass 40,000 for HTLV-I and 37,000 for HTLV-II1,2, located in the nucleus of infected cells3,4. HTLV-I is the causative agent of adult T-cell leukaemia (ATL), a T-lymphocyte malignancy5,6, while HTLV-II has been found associated with a T-cell variant of hairy cell leukaemia7,8. Both viruses immortalize T cells in vitro9–11. However, the mechanism of cellular transformation induced by HTLV is not known as there seems to be no common site of provirus integration in primary ATL cells12 and the viras contains no classical oncogene sequences13,14. These observations have provoked speculation that the unique and strongly conserved χ protein (85% amino-acid homology between HTLV-I and -II) is involved in HTLV leukaemogenesis. Recent mutagenesis experiments in our laboratory have shown that the χ gene is essential for HTLV replication15. It has also been shown that the LTRs of HTLV and the related bovine leukaemia virus (BLV) are activated in trans in virus-infected cells16–19, and, although such experiments did not directly demonstrate a role for the χ protein in transcriptional activation, it has been suggested that the χ protein is responsible for the transcriptional activation of the LTR and may be involved in cellular transformation3,4,16. We have now developed a transient co-transfection assay which demonstrates that transcriptional activation of the HTLV LTR is mediated solely by the χ protein and that no other virus genes are required.

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References

  1. Slamon, D. J., Shimotohno, K., Cline, M. J., Golde, D. W. & Chen, I. S. Y. Science 226, 61–65 (1984).

    Article  ADS  CAS  Google Scholar 

  2. Lee, T. H. et al. Science 226, 57–61 (1984).

    Article  ADS  CAS  Google Scholar 

  3. Goh, W. C., Sodroski, J., Rosen, C., Essex, M. & Haseltine, W. A. Science 227, 1227–1228 (1984).

    Article  ADS  Google Scholar 

  4. Slamon, D. J. et al. Science 228, 1427–1430 (1985).

    Article  ADS  CAS  Google Scholar 

  5. Gallo, R. C. et al. Cancer Res. 43, 3892–3899 (1983).

    CAS  PubMed  Google Scholar 

  6. Hinuma, Y. et al. Proc. natn, Acad. Sci. U.S.A. 78, 6476–6480 (1981).

    Article  ADS  CAS  Google Scholar 

  7. Kalyanaraman, V. S. et al. Science 218, 571–573 (1982).

    Article  ADS  CAS  Google Scholar 

  8. Saxon, A., Stevens, R. H. & Golde, D. W. Ann. intern. Med. 88, 323–326 (1978).

    Article  CAS  Google Scholar 

  9. Miyoshi, I. et al. Nature 294, 770–771 (1981).

    Article  ADS  CAS  Google Scholar 

  10. Chen, I. S. Y., Quan, S. G. & Golde, D. W. Proc. natn. Acad. Sci. U.S.A. 80, 7006–7009 (1983).

    Article  ADS  CAS  Google Scholar 

  11. Popovic, M., Lange-Wantzin, G., Savin, P. S., Mann, D. & Gallo, R. C. Proc. natn. Acad. Sci. U.S.A. 80, 5402–5406 (1983).

    Article  ADS  CAS  Google Scholar 

  12. Seiki, M., Eddy, R., Strows, T. B. & Yoshida, M. Nature 309, 640–642 (1984).

    Article  ADS  CAS  Google Scholar 

  13. Seiki, M., Hattori, S., Hirayma, Y. & Yoshida, M. Proc. natn. Acad. Sci. U.S.A. 80, 3618–3622 (1983).

    Article  ADS  CAS  Google Scholar 

  14. Shimotohno, K. et al. Proc. natn. Acad. Sci. U.S.A. 82, 3101–3105 (1985).

    Article  ADS  CAS  Google Scholar 

  15. Chen, I. S. Y. et al. Science 229, 54–58 (1985).

    Article  ADS  CAS  Google Scholar 

  16. Sodroski, J. G., Rosen, C. A. & Haseltine, W. A. Science 225, 381–385 (1984).

    Article  ADS  CAS  Google Scholar 

  17. Rosen, C. A., Kettman, R., Burny, A. & Haseltine, W. A. Science 227, 320–322 (1984).

    Article  ADS  Google Scholar 

  18. Derse, D., Caradonna, S. J. & Casey, J. W. Science 227, 317–320 (1985).

    Article  ADS  CAS  Google Scholar 

  19. Fujisawa, J., Seiki, M., Koyokawa, T. & Yoshida, M. Proc. natn. Acad. Sci. U.S.A. 82, 2277–2281 (1985).

    Article  ADS  CAS  Google Scholar 

  20. Chen, I. S. Y., McLaughlin, J., Gasson, J. C., Clark, S. C. & Golde, D. W. Nature 305, 502–505 (1983).

    Article  ADS  CAS  Google Scholar 

  21. Wachsman, W. et al. Science 228, 1534–1537 (1985).

    Article  ADS  CAS  Google Scholar 

  22. Chen, I. S. Y., McLaughlin, J. & Golde, D. W. Nature 309, 276–279 (1984).

    Article  ADS  CAS  Google Scholar 

  23. Broome, S. & Gilbert, W. Cell 40, 537–546 (1985).

    Article  CAS  Google Scholar 

  24. Varmus, H. E., Padgett, T., Heasley, S., Simon, G. & Bishop, J. M. Cell 11, 307–319 (1977).

    Article  CAS  Google Scholar 

  25. Chen, I. S. Y. & Temin, H. M. J. Virol. 41, 183–191 (1982).

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Jones, N. & Shenk, T. Proc. natn. Acad. Sci. U.S.A. 76, 3665–3669 (1979).

    Article  ADS  CAS  Google Scholar 

  27. Berk, A. J., Lee, F., Harrison, T., Williams, J. & Sharp, P. A. Cell 17, 935–944 (1979).

    Article  CAS  Google Scholar 

  28. Ruley, H. E. Nature 304, 602–606 (1983).

    Article  ADS  CAS  Google Scholar 

  29. Montell, C., Courtois, G., Eng, C. & Berk, A. Cell 36, 951–961 (1984).

    Article  CAS  Google Scholar 

  30. Ralston, R. & Bishop, J. M. Nature 306, 803–806 (1983).

    Article  ADS  CAS  Google Scholar 

  31. Chen, I. S. Y., Cann, A. J., Shah, N. P. & Gaynor, R. B. Science 230, 570–573 (1985).

    Article  ADS  CAS  Google Scholar 

  32. Land, H., Parada, L. F. & Weinberg, R. A. Science 222, 771–778 (1983).

    Article  ADS  CAS  Google Scholar 

  33. Kingston, R. E., Baldwin, S. & Sharp, P. A. Cell 41, 3 (1985).

    Article  CAS  Google Scholar 

  34. Southern, E. M. & Berg, P. J. molec. appl. Genet. 1, 327–341 (1982).

    CAS  Google Scholar 

  35. Mellon, P., Parker, V., Gluzman, Y. & Maniatis, T. Cell 27, 279–288 (1981).

    Article  CAS  Google Scholar 

  36. Gorman, C. M., Moffat, L. F. & Howard, B. H. Molec. Cell Biol. 2, 1044–1051 (1982).

    Article  CAS  Google Scholar 

  37. Chatis, P. A., Holland, C. A., Hartley, J. W., Rowe, W. P. & Hopkins, N. Proc. natn. Acad. Sci. U.S.A. 80, 4408–4411 (1983).

    Article  ADS  CAS  Google Scholar 

  38. Wachsman, W., Shimotohno, K., Clark, S. C., Golde, D. W. & Chen, I. S. Y. Science 226, 177–179 (1984).

    Article  ADS  CAS  Google Scholar 

  39. Felber, B. K., Paskelos, H., Kleinman-Ewing, C., Wong-Staal, F. & Pavlakis, G. N. Science 229, 675–679 (1985).

    Article  ADS  CAS  Google Scholar 

  40. Sodroski, J., Rosen, C., Goh, W. C. & Haseltine, W. Science 228, 1430–1434 (1985).

    Article  ADS  CAS  Google Scholar 

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Authors and Affiliations

  1. Division of Hematology-Oncology, Department of Medicine and Jonsson Comprehensive Cancer Center, UCLA School of Medicine, Los Angeles, California, 90024, USA

    Alan J. Cann, Joseph D. Rosenblatt, William Wachsman, Neil P. Shah & Irvin S. Y. Chen

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  1. Alan J. Cann
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  3. William Wachsman
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Cann, A., Rosenblatt, J., Wachsman, W. et al. Identification of the gene responsible for human T-cell leukaemia virus transcriptional regulation. Nature 318, 571–574 (1985). https://doi.org/10.1038/318571a0

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