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. 1984 Aug;81(15):4617–4621. doi: 10.1073/pnas.81.15.4617

Repetitive structure in the long-terminal-repeat element of a type II human T-cell leukemia virus.

J Sodroski, M Trus, D Perkins, R Patarca, F Wong-Staal, E Gelmann, R Gallo, W A Haseltine
PMCID: PMC391541  PMID: 6087335

Abstract

The majority of human T-cell leukemia virus isolates (HTLV-I) are associated with clinically aggressive adult T-cell leukemia/lymphomas. By contrast, HTLV-II has been isolated from a patient with a relatively benign hairy T-cell leukemia. To characterize differences in the viral genomes that might contribute to these different pathologies, we determined the nucleotide sequence of the long terminal repeat (LTR) of a HTLV-II provirus. Comparison with the type I HTLV LTR reveals that, whereas the overall structural features are similar, the two sequences differ markedly throughout most of the length of the LTR. Despite the overall differences, the sequences of several functional regions of the two LTRs are conserved. These include the 5' boundary of U3, the RNA cap site, and the tRNAPro-binding site immediately 3' to the LTR. Another point of similarity is a 21-base sequence that is repeated four times in the U3 region of HTLV-II and three times in the U3 region of HTLV-I. This sequence has a formal analogy to, but no common sequence with, viral transcriptional enhancers. The U3 region of HTLV-II possesses a series of imperfect tandem direct repeats, 42 bases long, 21 bases long, 19 bases long, and 7 bases long. These structures differ from those of HTLV-I except for the 21-base repeat sequence. Thus, the structure of HTLV-II differs substantially from that of HTLV-I in the region that governs transcriptional initiation and tissue specificity. Such differences may account for some of the differences in clinical presentation of HTLV-associated adult T-cell leukemia/lymphomas and hairy T-cell leukemia.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chatis P. A., Holland C. A., Hartley J. W., Rowe W. P., Hopkins N. Role for the 3' end of the genome in determining disease specificity of Friend and Moloney murine leukemia viruses. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4408–4411. doi: 10.1073/pnas.80.14.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Chen I. S., McLaughlin J., Gasson J. C., Clark S. C., Golde D. W. Molecular characterization of genome of a novel human T-cell leukaemia virus. Nature. 1983 Oct 6;305(5934):502–505. doi: 10.1038/305502a0. [DOI] [PubMed] [Google Scholar]
  3. Chen I. S., Quan S. G., Golde D. W. Human T-cell leukemia virus type II transforms normal human lymphocytes. Proc Natl Acad Sci U S A. 1983 Nov;80(22):7006–7009. doi: 10.1073/pnas.80.22.7006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Couez D., Deschamps J., Kettmann R., Stephens R. M., Gilden R. V., Burny A. Nucleotide sequence analysis of the long terminal repeat of integrated bovine leukemia provirus DNA and of adjacent viral and host sequences. J Virol. 1984 Feb;49(2):615–620. doi: 10.1128/jvi.49.2.615-620.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Czernilofsky A. P., DeLorbe W., Swanstrom R., Varmus H. E., Bishop J. M., Tischer E., Goodman H. M. The nucleotide sequence of an untranslated but conserved domain at the 3' end of the avian sarcoma virus genome. Nucleic Acids Res. 1980 Jul 11;8(13):2967–2984. doi: 10.1093/nar/8.13.2967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. DesGroseillers L., Rassart E., Jolicoeur P. Thymotropism of murine leukemia virus is conferred by its long terminal repeat. Proc Natl Acad Sci U S A. 1983 Jul;80(14):4203–4207. doi: 10.1073/pnas.80.14.4203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Efstratiadis A., Posakony J. W., Maniatis T., Lawn R. M., O'Connell C., Spritz R. A., DeRiel J. K., Forget B. G., Weissman S. M., Slightom J. L. The structure and evolution of the human beta-globin gene family. Cell. 1980 Oct;21(3):653–668. doi: 10.1016/0092-8674(80)90429-8. [DOI] [PubMed] [Google Scholar]
  8. Essex M., McLane M. F., Lee T. H., Falk L., Howe C. W., Mullins J. I., Cabradilla C., Francis D. P. Antibodies to cell membrane antigens associated with human T-cell leukemia virus in patients with AIDS. Science. 1983 May 20;220(4599):859–862. doi: 10.1126/science.6342136. [DOI] [PubMed] [Google Scholar]
  9. Gallo R. C., Sarin P. S., Gelmann E. P., Robert-Guroff M., Richardson E., Kalyanaraman V. S., Mann D., Sidhu G. D., Stahl R. E., Zolla-Pazner S. Isolation of human T-cell leukemia virus in acquired immune deficiency syndrome (AIDS). Science. 1983 May 20;220(4599):865–867. doi: 10.1126/science.6601823. [DOI] [PubMed] [Google Scholar]
  10. Gannon F., O'Hare K., Perrin F., LePennec J. P., Benoist C., Cochet M., Breathnach R., Royal A., Garapin A., Cami B. Organisation and sequences at the 5' end of a cloned complete ovalbumin gene. Nature. 1979 Mar 29;278(5703):428–434. doi: 10.1038/278428a0. [DOI] [PubMed] [Google Scholar]
  11. Gelmann E. P., Franchini G., Manzari V., Wong-Staal F., Gallo R. C. Molecular cloning of a unique human T-cell leukemia virus (HTLV-IIMo). Proc Natl Acad Sci U S A. 1984 Feb;81(4):993–997. doi: 10.1073/pnas.81.4.993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gelmann E. P., Popovic M., Blayney D., Masur H., Sidhu G., Stahl R. E., Gallo R. C. Proviral DNA of a retrovirus, human T-cell leukemia virus, in two patients with AIDS. Science. 1983 May 20;220(4599):862–865. doi: 10.1126/science.6601822. [DOI] [PubMed] [Google Scholar]
  13. Harada F., Peters G. G., Dahlberg J. E. The primer tRNA for Moloney murine leukemia virus DNA synthesis. Nucleotide sequence and aminoacylation of tRNAPro. J Biol Chem. 1979 Nov 10;254(21):10979–10985. [PubMed] [Google Scholar]
  14. Hinuma Y., Nagata K., Hanaoka M., Nakai M., Matsumoto T., Kinoshita K. I., Shirakawa S., Miyoshi I. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476–6480. doi: 10.1073/pnas.78.10.6476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kalyanaraman V. S., Sarngadharan M. G., Bunn P. A., Minna J. D., Gallo R. C. Antibodies in human sera reactive against an internal structural protein of human T-cell lymphoma virus. Nature. 1981 Nov 19;294(5838):271–273. doi: 10.1038/294271a0. [DOI] [PubMed] [Google Scholar]
  16. Kalyanaraman V. S., Sarngadharan M. G., Robert-Guroff M., Miyoshi I., Golde D., Gallo R. C. A new subtype of human T-cell leukemia virus (HTLV-II) associated with a T-cell variant of hairy cell leukemia. Science. 1982 Nov 5;218(4572):571–573. doi: 10.1126/science.6981847. [DOI] [PubMed] [Google Scholar]
  17. Lenz J., Haseltine W. A. Localization of the leukemogenic determinants of SL3-3, an ecotropic, XC-positive murine leukemia virus of AKR mouse origin. J Virol. 1983 Aug;47(2):317–328. doi: 10.1128/jvi.47.2.317-328.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Maxam A. M., Gilbert W. A new method for sequencing DNA. Proc Natl Acad Sci U S A. 1977 Feb;74(2):560–564. doi: 10.1073/pnas.74.2.560. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Miyoshi I., Kubonishi I., Yoshimoto S., Akagi T., Ohtsuki Y., Shiraishi Y., Nagata K., Hinuma Y. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature. 1981 Dec 24;294(5843):770–771. doi: 10.1038/294770a0. [DOI] [PubMed] [Google Scholar]
  20. Panganiban A. T., Temin H. M. The terminal nucleotides of retrovirus DNA are required for integration but not virus production. Nature. 1983 Nov 10;306(5939):155–160. doi: 10.1038/306155a0. [DOI] [PubMed] [Google Scholar]
  21. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415–7419. doi: 10.1073/pnas.77.12.7415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Poiesz B. J., Ruscetti F. W., Mier J. W., Woods A. M., Gallo R. C. T-cell lines established from human T-lymphocytic neoplasias by direct response to T-cell growth factor. Proc Natl Acad Sci U S A. 1980 Nov;77(11):6815–6819. doi: 10.1073/pnas.77.11.6815. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Popovic M., Sarin P. S., Robert-Gurroff M., Kalyanaraman V. S., Mann D., Minowada J., Gallo R. C. Isolation and transmission of human retrovirus (human t-cell leukemia virus). Science. 1983 Feb 18;219(4586):856–859. doi: 10.1126/science.6600519. [DOI] [PubMed] [Google Scholar]
  24. Proudfoot N. J., Brownlee G. G. Sequence at the 3' end of globin mRNA shows homology with immunoglobulin light chain mRNA. Nature. 1974 Nov 29;252(5482):359–362. doi: 10.1038/252359a0. [DOI] [PubMed] [Google Scholar]
  25. Reitz M. S., Jr, Popovic M., Haynes B. F., Clark S. C., Gallo R. C. Relatedness by nucleic acid hybridization of new isolates of human T-cell leukemia-lymphoma virus (HTLV) and demonstration of provirus in uncultured leukemic blood cells. Virology. 1983 Apr 30;126(2):688–672. doi: 10.1016/s0042-6822(83)80024-5. [DOI] [PubMed] [Google Scholar]
  26. Rho H. M., Poiesz B., Ruscetti F. W., Gallo R. C. Characterization of the reverse transcriptase from a new retrovirus (HTLV) produced by a human cutaneous T-cell lymphoma cell line. Virology. 1981 Jul 15;112(1):355–360. doi: 10.1016/0042-6822(81)90642-5. [DOI] [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Seiki M., Hattori S., Hirayama Y., Yoshida M. Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A. 1983 Jun;80(12):3618–3622. doi: 10.1073/pnas.80.12.3618. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Seiki M., Hattori S., Yoshida M. Human adult T-cell leukemia virus: molecular cloning of the provirus DNA and the unique terminal structure. Proc Natl Acad Sci U S A. 1982 Nov;79(22):6899–6902. doi: 10.1073/pnas.79.22.6899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Subramanian K. N., Dhar R., Weissman S. M. Nucleotide sequence of a fragment of SV40 DNA that contains the origin of DNA replication and specifies the 5' ends of "early" and "late" viral RNA. III. Construction of the total sequence of EcoRII-G fragment of SV40 DNA. J Biol Chem. 1977 Jan 10;252(1):355–367. [PubMed] [Google Scholar]
  31. Temin H. M. Function of the retrovirus long terminal repeat. Cell. 1982 Jan;28(1):3–5. doi: 10.1016/0092-8674(82)90367-1. [DOI] [PubMed] [Google Scholar]
  32. Temin H. M. Structure, variation and synthesis of retrovirus long terminal repeat. Cell. 1981 Nov;27(1 Pt 2):1–3. doi: 10.1016/0092-8674(81)90353-6. [DOI] [PubMed] [Google Scholar]
  33. Tsichlis P. N., Donehower L., Hager G., Zeller N., Malavarca R., Astrin S., Skalka A. M. Sequence comparison in the crossover region of an oncogenic avian retrovirus recombinant and its nononcogenic parent: genetic regions that control growth rate and oncogenic potential. Mol Cell Biol. 1982 Nov;2(11):1331–1338. doi: 10.1128/mcb.2.11.1331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Tsimanis A., Bichko V., Dreilina D., Meldrais J., Lozha V., Kukaine R., Gren E. The structure of cloned 3'-terminal RNA region of bovine leukemia virus (BLV). Nucleic Acids Res. 1983 Sep 10;11(17):6079–6087. doi: 10.1093/nar/11.17.6079. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Yamamoto N., Okada M., Koyanagi Y., Kannagi M., Hinuma Y. Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line. Science. 1982 Aug 20;217(4561):737–739. doi: 10.1126/science.6980467. [DOI] [PubMed] [Google Scholar]
  36. Yoshida M., Miyoshi I., Hinuma Y. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease. Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031–2035. doi: 10.1073/pnas.79.6.2031. [DOI] [PMC free article] [PubMed] [Google Scholar]

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