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. 1993 Feb;67(2):1015–1023. doi: 10.1128/jvi.67.2.1015-1023.1993

Complete nucleotide sequence of a highly divergent human T-cell leukemia (lymphotropic) virus type I (HTLV-I) variant from melanesia: genetic and phylogenetic relationship to HTLV-I strains from other geographical regions.

A Gessain 1, E Boeri 1, R Yanagihara 1, R C Gallo 1, G Franchini 1
PMCID: PMC237456  PMID: 8419636

Abstract

The high prevalences of antibodies against human T-cell leukemia (lymphotropic) virus type I (HTLV-I) reported for remote populations in Papua New Guinea and the Solomon Islands and for some aboriginal populations in Australia have been verified by virus isolation. Limited genetic analysis of the transmembrane portion (gp21) of the envelope gene of these viruses indicates the existence of highly divergent HTLV-I strains in Melanesia. Here, we report the complete nucleotide sequence of an HTLV-I isolate (designated HTLV-IMEL5) from the Solomon Islands. The overall nucleotide divergence of HTLV-IMEL5 from the prototype HTLV-IATK was approximately 8.5%. The degree of variability in the amino acid sequences of structural genes ranged between 3 and 11% and was higher (8.5 to 25%) for the regulatory (tax and rex) genes and the other genes encoded by the pX region. Since HTLV-IMEL5 was as distantly related to HTLV-II as to the other known HTLV-I strains, it could not have arisen from a reocmbinational event involving HTLV-II but rather might be an example of independent viral evolution in this remote population. These data provide important insights and raise new questions about the origin and global dissemination of HTLV-I.

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Selected References

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

  1. Ahmed Y. F., Hanly S. M., Malim M. H., Cullen B. R., Greene W. C. Structure-function analyses of the HTLV-I Rex and HIV-1 Rev RNA response elements: insights into the mechanism of Rex and Rev action. Genes Dev. 1990 Jun;4(6):1014–1022. doi: 10.1101/gad.4.6.1014. [DOI] [PubMed] [Google Scholar]
  2. Berneman Z. N., Gartenhaus R. B., Reitz M. S., Jr, Blattner W. A., Manns A., Hanchard B., Ikehara O., Gallo R. C., Klotman M. E. Expression of alternatively spliced human T-lymphotropic virus type I pX mRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia/lymphoma and healthy carriers. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):3005–3009. doi: 10.1073/pnas.89.7.3005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Cann A. J., Rosenblatt J. D., Wachsman W., Shah N. P., Chen I. S. Identification of the gene responsible for human T-cell leukaemia virus transcriptional regulation. Nature. 1985 Dec 12;318(6046):571–574. doi: 10.1038/318571a0. [DOI] [PubMed] [Google Scholar]
  4. Chen Y. M., Lee T. H., Samuel K. P., Okayama A., Tachibana N., Miyoshi I., Papas T. S., Essex M. Antibody reactivity to different regions of human T-cell leukemia virus type 1 gp61 in infected people. J Virol. 1989 Nov;63(11):4952–4957. doi: 10.1128/jvi.63.11.4952-4957.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Ciminale V., Pavlakis G. N., Derse D., Cunningham C. P., Felber B. K. Complex splicing in the human T-cell leukemia virus (HTLV) family of retroviruses: novel mRNAs and proteins produced by HTLV type I. J Virol. 1992 Mar;66(3):1737–1745. doi: 10.1128/jvi.66.3.1737-1745.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Copeland T. D., Tsai W. P., Kim Y. D., Oroszlan S. Envelope proteins of human T cell leukemia virus type I: characterization by antisera to synthetic peptides and identification of a natural epitope. J Immunol. 1986 Nov 1;137(9):2945–2951. [PubMed] [Google Scholar]
  7. 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]
  8. De B. K., Lairmore M. D., Griffis K., Williams L. J., Villinger F., Quinn T. C., Brown C., Nzilambi, Sugimoto M., Araki S. Comparative analysis of nucleotide sequences of the partial envelope gene (5' domain) among human T lymphotropic virus type I (HTLV-I) isolates. Virology. 1991 May;182(1):413–419. doi: 10.1016/0042-6822(91)90692-5. [DOI] [PubMed] [Google Scholar]
  9. Felber B. K., Derse D., Athanassopoulos A., Campbell M., Pavlakis G. N. Cross-activation of the Rex proteins of HTLV-I and BLV and of the Rev protein of HIV-1 and nonreciprocal interactions with their RNA responsive elements. New Biol. 1989 Dec;1(3):318–328. [PubMed] [Google Scholar]
  10. Felber B. K., Paskalis H., Kleinman-Ewing C., Wong-Staal F., Pavlakis G. N. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats. Science. 1985 Aug 16;229(4714):675–679. doi: 10.1126/science.2992082. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Gessain A., Gallo R. C., Franchini G. Low degree of human T-cell leukemia/lymphoma virus type I genetic drift in vivo as a means of monitoring viral transmission and movement of ancient human populations. J Virol. 1992 Apr;66(4):2288–2295. doi: 10.1128/jvi.66.4.2288-2295.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Gessian A., Yanagihara R., Franchini G., Garruto R. M., Jenkins C. L., Ajdukiewicz A. B., Gallo R. C., Gajdusek D. C. Highly divergent molecular variants of human T-lymphotropic virus type I from isolated populations in Papua New Guinea and the Solomon Islands. Proc Natl Acad Sci U S A. 1991 Sep 1;88(17):7694–7698. doi: 10.1073/pnas.88.17.7694. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Horal P., Hall W. W., Svennerholm B., Lycke J., Jeansson S., Rymo L., Kaplan M. H., Vahlne A. Identification of type-specific linear epitopes in the glycoproteins gp46 and gp21 of human T-cell leukemia viruses type I and type II using synthetic peptides. Proc Natl Acad Sci U S A. 1991 Jul 1;88(13):5754–5758. doi: 10.1073/pnas.88.13.5754. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Inoue J., Seiki M., Yoshida M. The second pX product p27 chi-III of HTLV-1 is required for gag gene expression. FEBS Lett. 1986 Dec 15;209(2):187–190. doi: 10.1016/0014-5793(86)81108-5. [DOI] [PubMed] [Google Scholar]
  17. Inoue J., Yoshida M., Seiki M. Transcriptional (p40x) and post-transcriptional (p27x-III) regulators are required for the expression and replication of human T-cell leukemia virus type I genes. Proc Natl Acad Sci U S A. 1987 Jun;84(11):3653–3657. doi: 10.1073/pnas.84.11.3653. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Jacobson S., Shida H., McFarlin D. E., Fauci A. S., Koenig S. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature. 1990 Nov 15;348(6298):245–248. doi: 10.1038/348245a0. [DOI] [PubMed] [Google Scholar]
  19. Kannagi M., Harada S., Maruyama I., Inoko H., Igarashi H., Kuwashima G., Sato S., Morita M., Kidokoro M., Sugimoto M. Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells. Int Immunol. 1991 Aug;3(8):761–767. doi: 10.1093/intimm/3.8.761. [DOI] [PubMed] [Google Scholar]
  20. Kiyokawa T., Seiki M., Iwashita S., Imagawa K., Shimizu F., Yoshida M. p27x-III and p21x-III, proteins encoded by the pX sequence of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1985 Dec;82(24):8359–8363. doi: 10.1073/pnas.82.24.8359. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Komurian F., Pelloquin F., de Thé G. In vivo genomic variability of human T-cell leukemia virus type I depends more upon geography than upon pathologies. J Virol. 1991 Jul;65(7):3770–3778. doi: 10.1128/jvi.65.7.3770-3778.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Koralnik I. J., Gessain A., Klotman M. E., Lo Monico A., Berneman Z. N., Franchini G. Protein isoforms encoded by the pX region of human T-cell leukemia/lymphotropic virus type I. Proc Natl Acad Sci U S A. 1992 Sep 15;89(18):8813–8817. doi: 10.1073/pnas.89.18.8813. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kurata A., Palker T. J., Streilein R. D., Scearce R. M., Haynes B. F., Berzofsky J. A. Immunodominant sites of human T cell lymphotropic virus type 1 envelope protein for murine helper T cells. J Immunol. 1989 Sep 15;143(6):2024–2030. [PubMed] [Google Scholar]
  24. Lal R. B., Rudolph D. L., Griffis K. P., Kitamura K., Honda M., Coligan J. E., Folks T. M. Characterization of immunodominant epitopes of gag and pol gene-encoded proteins of human T-cell lymphotropic virus type I. J Virol. 1991 Apr;65(4):1870–1876. doi: 10.1128/jvi.65.4.1870-1876.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Matsushita S., Robert-Guroff M., Trepel J., Cossman J., Mitsuya H., Broder S. Human monoclonal antibody directed against an envelope glycoprotein of human T-cell leukemia virus type I. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2672–2676. doi: 10.1073/pnas.83.8.2672. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Nagashima K., Yoshida M., Seiki M. A single species of pX mRNA of human T-cell leukemia virus type I encodes trans-activator p40x and two other phosphoproteins. J Virol. 1986 Nov;60(2):394–399. doi: 10.1128/jvi.60.2.394-399.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nosaka T., Siomi H., Adachi Y., Ishibashi M., Kubota S., Maki M., Hatanaka M. Nucleolar targeting signal of human T-cell leukemia virus type I rex-encoded protein is essential for cytoplasmic accumulation of unspliced viral mRNA. Proc Natl Acad Sci U S A. 1989 Dec;86(24):9798–9802. doi: 10.1073/pnas.86.24.9798. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Paine E., Garcia J., Philpott T. C., Shaw G., Ratner L. Limited sequence variation in human T-lymphotropic virus type 1 isolates from North American and African patients. Virology. 1991 May;182(1):111–123. doi: 10.1016/0042-6822(91)90654-t. [DOI] [PubMed] [Google Scholar]
  29. Palker T. J., Riggs E. R., Spragion D. E., Muir A. J., Scearce R. M., Randall R. R., McAdams M. W., McKnight A., Clapham P. R., Weiss R. A. Mapping of homologous, amino-terminal neutralizing regions of human T-cell lymphotropic virus type I and II gp46 envelope glycoproteins. J Virol. 1992 Oct;66(10):5879–5889. doi: 10.1128/jvi.66.10.5879-5889.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Palker T. J., Tanner M. E., Scearce R. M., Streilein R. D., Clark M. E., Haynes B. F. Mapping of immunogenic regions of human T cell leukemia virus type I (HTLV-I) gp46 and gp21 envelope glycoproteins with env-encoded synthetic peptides and a monoclonal antibody to gp46. J Immunol. 1989 Feb 1;142(3):971–978. [PubMed] [Google Scholar]
  31. 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]
  32. Ralston S., Hoeprich P., Akita R. Identification and synthesis of the epitope for a human monoclonal antibody which can neutralize human T-cell leukemia/lymphotropic virus type I. J Biol Chem. 1989 Oct 5;264(28):16343–16346. [PubMed] [Google Scholar]
  33. Ratner L., Philpott T., Trowbridge D. B. Nucleotide sequence analysis of isolates of human T-lymphotropic virus type 1 of diverse geographical origins. AIDS Res Hum Retroviruses. 1991 Nov;7(11):923–941. doi: 10.1089/aid.1991.7.923. [DOI] [PubMed] [Google Scholar]
  34. Schulz T. F., Calabrò M. L., Hoad J. G., Carrington C. V., Matutes E., Catovsky D., Weiss R. A. HTLV-1 envelope sequences from Brazil, the Caribbean, and Romania: clustering of sequences according to geographic origin and variability in an antibody epitope. Virology. 1991 Oct;184(2):483–491. doi: 10.1016/0042-6822(91)90418-b. [DOI] [PubMed] [Google Scholar]
  35. 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]
  36. Sherman M. P., Saksena N. K., Dube D. K., Yanagihara R., Poiesz B. J. Evolutionary insights on the origin of human T-cell lymphoma/leukemia virus type I (HTLV-I) derived from sequence analysis of a new HTLV-I variant from Papua New Guinea. J Virol. 1992 Apr;66(4):2556–2563. doi: 10.1128/jvi.66.4.2556-2563.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Shimotohno K., Takahashi Y., Shimizu N., Gojobori T., Golde D. W., Chen I. S., Miwa M., Sugimura T. Complete nucleotide sequence of an infectious clone of human T-cell leukemia virus type II: an open reading frame for the protease gene. Proc Natl Acad Sci U S A. 1985 May;82(10):3101–3105. doi: 10.1073/pnas.82.10.3101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Shirabe S., Nakamura T., Tsujihata M., Nagataki S., Seiki M., Yoshida M. Retrovirus from human T-cell leukemia virus type I-associated myelopathy is the same strain as a prototype human T-cell leukemia virus type I. Arch Neurol. 1990 Nov;47(11):1258–1260. doi: 10.1001/archneur.1990.00530110120029. [DOI] [PubMed] [Google Scholar]
  39. Siomi H., Shida H., Nam S. H., Nosaka T., Maki M., Hatanaka M. Sequence requirements for nucleolar localization of human T cell leukemia virus type I pX protein, which regulates viral RNA processing. Cell. 1988 Oct 21;55(2):197–209. doi: 10.1016/0092-8674(88)90043-8. [DOI] [PubMed] [Google Scholar]
  40. Sodroski J., Rosen C., Goh W. C., Haseltine W. A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus. Science. 1985 Jun 21;228(4706):1430–1434. doi: 10.1126/science.2990028. [DOI] [PubMed] [Google Scholar]
  41. Tanaka Y., Zeng L., Shiraki H., Shida H., Tozawa H. Identification of a neutralization epitope on the envelope gp46 antigen of human T cell leukemia virus type I and induction of neutralizing antibody by peptide immunization. J Immunol. 1991 Jul 1;147(1):354–360. [PubMed] [Google Scholar]
  42. 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]
  43. Yanagihara R., Nerukar V. R., Ajdukiewicz A. B. Comparison between strains of human T lymphotropic virus type I isolated from inhabitants of the Solomon Islands and Papua New Guinea. J Infect Dis. 1991 Sep;164(3):443–449. doi: 10.1093/infdis/164.3.443. [DOI] [PubMed] [Google Scholar]
  44. Yanagihara R., Nerurkar V. R., Garruto R. M., Miller M. A., Leon-Monzon M. E., Jenkins C. L., Sanders R. C., Liberski P. P., Alpers M. P., Gajdusek D. C. Characterization of a variant of human T-lymphotropic virus type I isolated from a healthy member of a remote, recently contacted group in Papua New Guinea. Proc Natl Acad Sci U S A. 1991 Feb 15;88(4):1446–1450. doi: 10.1073/pnas.88.4.1446. [DOI] [PMC free article] [PubMed] [Google Scholar]

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