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. 1991 Jul;65(7):3770–3778. doi: 10.1128/jvi.65.7.3770-3778.1991

In vivo genomic variability of human T-cell leukemia virus type I depends more upon geography than upon pathologies.

F Komurian 1, F Pelloquin 1, G de Thé 1
PMCID: PMC241407  PMID: 2041093

Abstract

To investigate the geography- and disease-associated genomic variation of human T-cell leukemia virus type I (HTLV-I), we studied ex vivo DNA from peripheral blood lymphocytes from nine patients by polymerase chain reaction and direct DNA sequencing. For each viral strain, 1,917 bp was sequenced, including parts of the long terminal repeat, the env gene, and the px II, px III, and px IV coding frames of the px region. The number of genomic variations observed in the U3 region of the long terminal repeat was higher than that seen in the env and px genes. Very few mutations were present in the px II and px III genes. In contrast, the px IV open reading frame exhibited numerous single point mutations. While no specific mutation could be linked to any pathology (adult T-cell leukemia/lymphoma or tropical spastic paraparesis/HTLV-I-associated myelopathy), variations among HTLV-I isolates from different geographic areas (Ivory Coast, Caribbean, and Japan) existed. The Ivory Coast HTLV-I appeared to represent a group by itself.

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Selected References

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  1. Bangham C. R., Daenke S., Phillips R. E., Cruickshank J. K., Bell J. I. Enzymatic amplification of exogenous and endogenous retroviral sequences from DNA of patients with tropical spastic paraparesis. EMBO J. 1988 Dec 20;7(13):4179–4184. doi: 10.1002/j.1460-2075.1988.tb03314.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Blattner W. A., Kalyanaraman V. S., Robert-Guroff M., Lister T. A., Galton D. A., Sarin P. S., Crawford M. H., Catovsky D., Greaves M., Gallo R. C. The human type-C retrovirus, HTLV, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma. Int J Cancer. 1982 Sep 15;30(3):257–264. doi: 10.1002/ijc.2910300302. [DOI] [PubMed] [Google Scholar]
  3. Bosselut R., Duvall J. F., Gégonne A., Bailly M., Hémar A., Brady J., Ghysdael J. The product of the c-ets-1 proto-oncogene and the related Ets2 protein act as transcriptional activators of the long terminal repeat of human T cell leukemia virus HTLV-1. EMBO J. 1990 Oct;9(10):3137–3144. doi: 10.1002/j.1460-2075.1990.tb07511.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Brady J., Jeang K. T., Duvall J., Khoury G. Identification of p40x-responsive regulatory sequences within the human T-cell leukemia virus type I long terminal repeat. J Virol. 1987 Jul;61(7):2175–2181. doi: 10.1128/jvi.61.7.2175-2181.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Böhnlein E., Siekevitz M., Ballard D. W., Lowenthal J. W., Rimsky L., Bogérd H., Hoffman J., Wano Y., Franza B. R., Greene W. C. Stimulation of the human immunodeficiency virus type 1 enhancer by the human T-cell leukemia virus type I tax gene product involves the action of inducible cellular proteins. J Virol. 1989 Apr;63(4):1578–1586. doi: 10.1128/jvi.63.4.1578-1586.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cann A. J., Rosenblatt J. D., Wachsman W., Chen I. S. In vitro mutagenesis of the human T-cell leukemia virus types I and II tax genes. J Virol. 1989 Mar;63(3):1474–1479. doi: 10.1128/jvi.63.3.1474-1479.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cianciolo G. J., Kipnis R. J., Snyderman R. Similarity between p15E of murine and feline leukaemia viruses and p21 of HTLV. Nature. 1984 Oct 11;311(5986):515–515. doi: 10.1038/311515a0. [DOI] [PubMed] [Google Scholar]
  8. Daenke S., Nightingale S., Cruickshank J. K., Bangham C. R. Sequence variants of human T-cell lymphotropic virus type I from patients with tropical spastic paraparesis and adult T-cell leukemia do not distinguish neurological from leukemic isolates. J Virol. 1990 Mar;64(3):1278–1282. doi: 10.1128/jvi.64.3.1278-1282.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fox H. B., Gutman P. D., Dave H. P., Cao S. X., Mittelman M., Berg P. E., Schechter A. N. Trans-activation of human globin genes by HTLV-I tax1. Blood. 1989 Dec;74(8):2749–2754. [PubMed] [Google Scholar]
  10. Fujisawa J., Seiki M., Sato M., Yoshida M. A transcriptional enhancer sequence of HTLV-I is responsible for trans-activation mediated by p40 chi HTLV-I. EMBO J. 1986 Apr;5(4):713–718. doi: 10.1002/j.1460-2075.1986.tb04272.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Fujisawa J., Toita M., Yoshida M. A unique enhancer element for the trans activator (p40tax) of human T-cell leukemia virus type I that is distinct from cyclic AMP- and 12-O-tetradecanoylphorbol-13-acetate-responsive elements. J Virol. 1989 Aug;63(8):3234–3239. doi: 10.1128/jvi.63.8.3234-3239.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Gessain A., Barin F., Vernant J. C., Gout O., Maurs L., Calender A., de Thé G. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet. 1985 Aug 24;2(8452):407–410. doi: 10.1016/s0140-6736(85)92734-5. [DOI] [PubMed] [Google Scholar]
  13. Gessain A., Gout O., Saal F., Daniel M. T., Rio B., Flandrin G., Sigaux F., Lyon-Caen O., Periès J., de-Thé G. Epidemiology and immunovirology of human T-cell leukemia/lymphoma virus type I-associated adult T-cell leukemia and chronic myelopathies as seen in France. Cancer Res. 1990 Sep 1;50(17 Suppl):5692S–5696S. [PubMed] [Google Scholar]
  14. Giam C. Z., Xu Y. L. HTLV-I tax gene product activates transcription via pre-existing cellular factors and cAMP responsive element. J Biol Chem. 1989 Sep 15;264(26):15236–15241. [PubMed] [Google Scholar]
  15. Goodenow M., Huet T., Saurin W., Kwok S., Sninsky J., Wain-Hobson S. HIV-1 isolates are rapidly evolving quasispecies: evidence for viral mixtures and preferred nucleotide substitutions. J Acquir Immune Defic Syndr. 1989;2(4):344–352. [PubMed] [Google Scholar]
  16. Gray G. S., White M., Bartman T., Mann D. Envelope gene sequence of HTLV-1 isolate MT-2 and its comparison with other HTLV-1 isolates. Virology. 1990 Jul;177(1):391–395. doi: 10.1016/0042-6822(90)90498-g. [DOI] [PubMed] [Google Scholar]
  17. Green J. E., Begley C. G., Wagner D. K., Waldmann T. A., Jay G. trans activation of granulocyte-macrophage colony-stimulating factor and the interleukin-2 receptor in transgenic mice carrying the human T-lymphotropic virus type 1 tax gene. Mol Cell Biol. 1989 Nov;9(11):4731–4737. doi: 10.1128/mcb.9.11.4731. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Hidaka M., Inoue J., Yoshida M., Seiki M. Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins. EMBO J. 1988 Feb;7(2):519–523. doi: 10.1002/j.1460-2075.1988.tb02840.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Jeang K. T., Boros I., Brady J., Radonovich M., Khoury G. Characterization of cellular factors that interact with the human T-cell leukemia virus type I p40x-responsive 21-base-pair sequence. J Virol. 1988 Dec;62(12):4499–4509. doi: 10.1128/jvi.62.12.4499-4509.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Josephs S. F., Wong-Staal F., Manzari V., Gallo R. C., Sodroski J. G., Trus M. D., Perkins D., Patarca R., Haseltine W. A. Long terminal repeat structure of an American isolate of type I human T-cell leukemia virus. Virology. 1984 Dec;139(2):340–345. doi: 10.1016/0042-6822(84)90379-9. [DOI] [PubMed] [Google Scholar]
  22. Lefrère J. J., Couroucé A. M., Mariotti M., Wattel E., Prou O., Bouchardeau F., Lambin P. Rapid progression to AIDS in dual HIV-1/HTLV-I infection. Lancet. 1990 Aug 25;336(8713):509–509. doi: 10.1016/0140-6736(90)92060-u. [DOI] [PubMed] [Google Scholar]
  23. Lenz J., Celander D., Crowther R. L., Patarca R., Perkins D. W., Haseltine W. A. Determination of the leukaemogenicity of a murine retrovirus by sequences within the long terminal repeat. 1984 Mar 29-Apr 4Nature. 308(5958):467–470. doi: 10.1038/308467a0. [DOI] [PubMed] [Google Scholar]
  24. Li Y., Golemis E., Hartley J. W., Hopkins N. Disease specificity of nondefective Friend and Moloney murine leukemia viruses is controlled by a small number of nucleotides. J Virol. 1987 Mar;61(3):693–700. doi: 10.1128/jvi.61.3.693-700.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. LoSardo J. E., Cupelli L. A., Short M. K., Berman J. W., Lenz J. Differences in activities of murine retroviral long terminal repeats in cytotoxic T lymphocytes and T-lymphoma cells. J Virol. 1989 Mar;63(3):1087–1094. doi: 10.1128/jvi.63.3.1087-1094.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Malik K. T., Even J., Karpas A. Molecular cloning and complete nucleotide sequence of an adult T cell leukaemia virus/human T cell leukaemia virus type I (ATLV/HTLV-I) isolate of Caribbean origin: relationship to other members of the ATLV/HTLV-I subgroup. J Gen Virol. 1988 Jul;69(Pt 7):1695–1710. doi: 10.1099/0022-1317-69-7-1695. [DOI] [PubMed] [Google Scholar]
  27. Marriott S. J., Boros I., Duvall J. F., Brady J. N. Indirect binding of human T-cell leukemia virus type I tax1 to a responsive element in the viral long terminal repeat. Mol Cell Biol. 1989 Oct;9(10):4152–4160. doi: 10.1128/mcb.9.10.4152. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Marriott S. J., Lindholm P. F., Brown K. M., Gitlin S. D., Duvall J. F., Radonovich M. F., Brady J. N. A 36-kilodalton cellular transcription factor mediates an indirect interaction of human T-cell leukemia/lymphoma virus type I TAX1 with a responsive element in the viral long terminal repeat. Mol Cell Biol. 1990 Aug;10(8):4192–4201. doi: 10.1128/mcb.10.8.4192. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Nimer S. D., Gasson J. C., Hu K., Smalberg I., Williams J. L., Chen I. S., Rosenblatt J. D. Activation of the GM-CSF promoter by HTLV-I and -II tax proteins. Oncogene. 1989 Jun;4(6):671–676. [PubMed] [Google Scholar]
  30. Nyborg J. K., Dynan W. S., Chen I. S., Wachsman W. Binding of host-cell factors to DNA sequences in the long terminal repeat of human T-cell leukemia virus type I: implications for viral gene expression. Proc Natl Acad Sci U S A. 1988 Mar;85(5):1457–1461. doi: 10.1073/pnas.85.5.1457. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Osame M., Usuku K., Izumo S., Ijichi N., Amitani H., Igata A., Matsumoto M., Tara M. HTLV-I associated myelopathy, a new clinical entity. Lancet. 1986 May 3;1(8488):1031–1032. doi: 10.1016/s0140-6736(86)91298-5. [DOI] [PubMed] [Google Scholar]
  32. Page J. B., Lai S. H., Chitwood D. D., Klimas N. G., Smith P. C., Fletcher M. A. HTLV-I/II seropositivity and death from AIDS among HIV-1 seropositive intravenous drug users. Lancet. 1990 Jun 16;335(8703):1439–1441. doi: 10.1016/0140-6736(90)91456-k. [DOI] [PubMed] [Google Scholar]
  33. 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]
  34. Poteat H. T., Kadison P., McGuire K., Park L., Park R. E., Sodroski J. G., Haseltine W. A. Response of the human T-cell leukemia virus type 1 long terminal repeat to cyclic AMP. J Virol. 1989 Apr;63(4):1604–1611. doi: 10.1128/jvi.63.4.1604-1611.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Radonovich M., Jeang K. T. Activation of the human T-cell leukemia virus type I long terminal repeat by 12-O-tetradecanoylphorbol-13-acetate and by tax (p40x) occurs through similar but functionally distinct target sequences. J Virol. 1989 Jul;63(7):2987–2994. doi: 10.1128/jvi.63.7.2987-2994.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  36. Rassart E., Nelbach L., Jolicoeur P. Cas-Br-E murine leukemia virus: sequencing of the paralytogenic region of its genome and derivation of specific probes to study its origin and the structure of its recombinant genomes in leukemic tissues. J Virol. 1986 Dec;60(3):910–919. doi: 10.1128/jvi.60.3.910-919.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Ratner L., Josephs S. F., Starcich B., Hahn B., Shaw G. M., Gallo R. C., Wong-Staal F. Nucleotide sequence analysis of a variant human T-cell leukemia virus (HTLV-Ib) provirus with a deletion in pX-I. J Virol. 1985 Jun;54(3):781–790. doi: 10.1128/jvi.54.3.781-790.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Reddy E. P., Sandberg-Wollheim M., Mettus R. V., Ray P. E., DeFreitas E., Koprowski H. Amplification and molecular cloning of HTLV-I sequences from DNA of multiple sclerosis patients. Science. 1989 Jan 27;243(4890):529–533. doi: 10.1126/science.2536193. [DOI] [PubMed] [Google Scholar]
  39. Rosen C. A., Park R., Sodroski J. G., Haseltine W. A. Multiple sequence elements are required for regulation of human T-cell leukemia virus gene expression. Proc Natl Acad Sci U S A. 1987 Jul;84(14):4919–4923. doi: 10.1073/pnas.84.14.4919. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Ruben S., Poteat H., Tan T. H., Kawakami K., Roeder R., Haseltine W., Rosen C. A. Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product. Science. 1988 Jul 1;241(4861):89–92. doi: 10.1126/science.2838905. [DOI] [PubMed] [Google Scholar]
  41. 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]
  42. 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]
  43. Seiki M., Inoue J., Takeda T., Yoshida M. Direct evidence that p40x of human T-cell leukemia virus type I is a trans-acting transcriptional activator. EMBO J. 1986 Mar;5(3):561–565. doi: 10.1002/j.1460-2075.1986.tb04247.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Srinivasan A., York D., Jannoun-Nasr R., Kalyanaraman S., Swan D., Benson J., Bohan C., Luciw P. A., Schnoll S., Robinson R. A. Generation of hybrid human immunodeficiency virus by homologous recombination. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6388–6392. doi: 10.1073/pnas.86.16.6388. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Szurek P. F., Yuen P. H., Jerzy R., Wong P. K. Identification of point mutations in the envelope gene of Moloney murine leukemia virus TB temperature-sensitive paralytogenic mutant ts1: molecular determinants for neurovirulence. J Virol. 1988 Jan;62(1):357–360. doi: 10.1128/jvi.62.1.357-360.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Tan T. H., Horikoshi M., Roeder R. G. Purification and characterization of multiple nuclear factors that bind to the TAX-inducible enhancer within the human T-cell leukemia virus type 1 long terminal repeat. Mol Cell Biol. 1989 Apr;9(4):1733–1745. doi: 10.1128/mcb.9.4.1733. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Tsujimoto A., Teruuchi T., Imamura J., Shimotohno K., Miyoshi I., Miwa M. Nucleotide sequence analysis of a provirus derived from HTLV-1-associated myelopathy (HAM). Mol Biol Med. 1988 Feb;5(1):29–42. [PubMed] [Google Scholar]
  48. Usuku K., Sonoda S., Osame M., Yashiki S., Takahashi K., Matsumoto M., Sawada T., Tsuji K., Tara M., Igata A. HLA haplotype-linked high immune responsiveness against HTLV-I in HTLV-I-associated myelopathy: comparison with adult T-cell leukemia/lymphoma. Ann Neurol. 1988;23 (Suppl):S143–S150. doi: 10.1002/ana.410230733. [DOI] [PubMed] [Google Scholar]
  49. Yamamoto N., Hinuma Y. Viral aetiology of adult T-cell leukaemia. J Gen Virol. 1985 Aug;66(Pt 8):1641–1660. doi: 10.1099/0022-1317-66-8-1641. [DOI] [PubMed] [Google Scholar]
  50. Yokota T., Cho M. J., Tachibana N., McLane M. F., Takatsuki K., Lee T. H., Mueller N., Essex M. The prevalence of antibody to p42 of HTLV-I among ATLL patients in comparison with healthy carriers in Japan. Int J Cancer. 1989 Jun 15;43(6):970–974. doi: 10.1002/ijc.2910430603. [DOI] [PubMed] [Google Scholar]
  51. Yoshimura T., Fujisawa J., Yoshida M. Multiple cDNA clones encoding nuclear proteins that bind to the tax-dependent enhancer of HTLV-1: all contain a leucine zipper structure and basic amino acid domain. EMBO J. 1990 Aug;9(8):2537–2542. doi: 10.1002/j.1460-2075.1990.tb07434.x. [DOI] [PMC free article] [PubMed] [Google Scholar]

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