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MeSH Review

Human T-lymphotropic virus 1

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Disease relevance of Human T-lymphotropic virus 1


High impact information on Human T-lymphotropic virus 1

  • We show that the receptor binding domains of both HTLV-1 and -2 envelope glycoproteins inhibit glucose transport by interacting with GLUT-1, the ubiquitous vertebrate glucose transporter [6].
  • In searching for cellular targets of the HTLV-I oncoprotein Tax, we identified TXBP181, which we characterized as the human homolog of yeast mitotic checkpoint MAD1 protein [7].
  • HTLV-I Tax protein binds to MEKK1 to stimulate IkappaB kinase activity and NF-kappaB activation [8].
  • Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I [9].
  • The viral Tax protein, which is encoded by human T-cell leukaemia virus HTLV-I, activates nuclear translocation of the NF-kappa B/Rel transcription factors and relieves cytoplasmic sequestration of RelA and Rel by heterodimerization with NF-kappa B1/p1O5 (refs 1,2) [10].

Chemical compound and disease context of Human T-lymphotropic virus 1

  • The structure of the A6 alphabetaTCR/HTLV-1 Tax-peptide/MHC I complex with proline 6 of Tax substituted with alanine (P6A), an antagonist, is nearly identical to the structure with wild-type Tax agonist [11].
  • Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells [12].
  • Hydrocortisone, a drug effective in vivo for the treatment of HTLV-I uveitis, severely depressed cytokine production in vitro in most cases [13].
  • Recombinant protein (RP) B1 contains aminoacids 166-201 from HTLV-I exterior glycoprotein gp46 and was reactive with HTLV-I samples only [14].
  • By using a competition assay with a biotin-labeled 0.5 alpha antibody, we observed that 15 out of 15 patients with adult T-cell leukemia had antibodies that block binding of the 0.5 alpha antibody to HTLV-I virions [15].

Biological context of Human T-lymphotropic virus 1


Anatomical context of Human T-lymphotropic virus 1

  • Cell lines infected by HTLV-I express levels of TCR beta mRNA similar to PHA stimulated lymphocytes, suggesting that this gene is not transcriptionally activated as a result of infection by HTLV-I [20].
  • The collective evidence indicates that the endogenous IL-2 receptor gene is activated in human and rat lymphoid cell lines with HTLV-I production [21].
  • The present results suggest that T cells containing restricted V beta CDR3 motifs, which are also found in MS and EAE, become activated upon HTLV-I infection and infiltrate into the spinal cord lesions of HAM/TSP patients [22].
  • This study demonstrates that HTLV-I can directly infect normal mature human B cells, and that the Tac antigen, which may be induced by infection with HTLV-I, is the functional receptor for IL-2-induced B cell differentiation [23].
  • In contrast, no sample from 32 patients with uncomplicated rheumatoid arthritis, 27 with Felty's syndrome, 11 with other connective tissue disorders, or 21 normal individuals reacted with HTLV-I [24].

Gene context of Human T-lymphotropic virus 1

  • STAT3 expression in particular has been associated with Abl, Src, and HTLV-1 transformation of normal cells [25].
  • These results, taken together with those on normal IL-2 receptors on HTLV-I-negative T-CLL cells, suggest that abnormal expression of the IL-2 receptor in ATL is closely associated with HTLV-I infection and may play a role in the neoplastic growth of ATL cells [26].
  • HTLV-I-infected TCC, but not HTLV-I negative TCC, constitutively produced high amounts of IL-6 (1,336 +/- 1,050 pg/ml) and TNF-alpha (289 +/- 237 pg/ml) in the absence of any stimuli [13].
  • HTLV-1 Tax protein interacts with cyclin-dependent kinase inhibitor p16INK4A and counteracts its inhibitory activity towards CDK4 [27].
  • Activation of the IL-2 gene promoter by HTLV-I tax involves induction of NF-AT complexes bound to the CD28-responsive element [28].

Analytical, diagnostic and therapeutic context of Human T-lymphotropic virus 1


  1. Functional replacement of the HIV-1 rev protein by the HTLV-1 rex protein. Rimsky, L., Hauber, J., Dukovich, M., Malim, M.H., Langlois, A., Cullen, B.R., Greene, W.C. Nature (1988) [Pubmed]
  2. Diagnostic potential for human malignancies of bacterially produced HTLV-I envelope protein. Samuel, K.P., Lautenberger, J.A., Jorcyk, C.L., Josephs, S., Wong-Staal, F., Papas, T.S. Science (1984) [Pubmed]
  3. Activation of the HIV-1 LTR by T cell mitogens and the trans-activator protein of HTLV-I. Siekevitz, M., Josephs, S.F., Dukovich, M., Peffer, N., Wong-Staal, F., Greene, W.C. Science (1987) [Pubmed]
  4. Characterization of long terminal repeat sequences of HTLV-III. Starcich, B., Ratner, L., Josephs, S.F., Okamoto, T., Gallo, R.C., Wong-Staal, F. Science (1985) [Pubmed]
  5. Serological analysis of a subgroup of human T-lymphotropic retroviruses (HTLV-III) associated with AIDS. Schüpbach, J., Popovic, M., Gilden, R.V., Gonda, M.A., Sarngadharan, M.G., Gallo, R.C. Science (1984) [Pubmed]
  6. The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV. Manel, N., Kim, F.J., Kinet, S., Taylor, N., Sitbon, M., Battini, J.L. Cell (2003) [Pubmed]
  7. Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Jin, D.Y., Spencer, F., Jeang, K.T. Cell (1998) [Pubmed]
  8. HTLV-I Tax protein binds to MEKK1 to stimulate IkappaB kinase activity and NF-kappaB activation. Yin, M.J., Christerson, L.B., Yamamoto, Y., Kwak, Y.T., Xu, S., Mercurio, F., Barbosa, M., Cobb, M.H., Gaynor, R.B. Cell (1998) [Pubmed]
  9. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I. Cross, S.L., Feinberg, M.B., Wolf, J.B., Holbrook, N.J., Wong-Staal, F., Leonard, W.J. Cell (1987) [Pubmed]
  10. Effects on NF-kappa B1/p105 processing of the interaction between the HTLV-1 transactivator Tax and the proteasome. Rousset, R., Desbois, C., Bantignies, F., Jalinot, P. Nature (1996) [Pubmed]
  11. Conversion of a T cell antagonist into an agonist by repairing a defect in the TCR/peptide/MHC interface: implications for TCR signaling. Baker, B.M., Gagnon, S.J., Biddison, W.E., Wiley, D.C. Immunity (2000) [Pubmed]
  12. Constitutive activation of different Jak tyrosine kinases in human T cell leukemia virus type 1 (HTLV-1) tax protein or virus-transformed cells. Xu, X., Kang, S.H., Heidenreich, O., Okerholm, M., O'Shea, J.J., Nerenberg, M.I. J. Clin. Invest. (1995) [Pubmed]
  13. Immunopathological mechanisms of human T cell lymphotropic virus type 1 (HTLV-I) uveitis. Detection of HTLV-I-infected T cells in the eye and their constitutive cytokine production. Sagawa, K., Mochizuki, M., Masuoka, K., Katagiri, K., Katayama, T., Maeda, T., Tanimoto, A., Sugita, S., Watanabe, T., Itoh, K. J. Clin. Invest. (1995) [Pubmed]
  14. Type-specific antigens for serological discrimination of HTLV-I and HTLV-II infection. Chen, Y.M., Lee, T.H., Wiktor, S.Z., Shaw, G.M., Murphy, E.L., Blattner, W.A., Essex, M. Lancet (1990) [Pubmed]
  15. Human monoclonal antibody directed against an envelope glycoprotein of human T-cell leukemia virus type I. Matsushita, S., Robert-Guroff, M., Trepel, J., Cossman, J., Mitsuya, H., Broder, S. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  16. U3 sequences from HTLV-I and -II LTRs confer pX protein response to a murine leukemia virus LTR. Kitado, H., Chen, I.S., Shah, N.P., Cann, A.J., Shimotohno, K., Fan, H. Science (1987) [Pubmed]
  17. Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product. Ruben, S., Poteat, H., Tan, T.H., Kawakami, K., Roeder, R., Haseltine, W., Rosen, C.A. Science (1988) [Pubmed]
  18. Comparative analysis of the HTLV-I Rex and HIV-1 Rev trans-regulatory proteins and their RNA response elements. Hanly, S.M., Rimsky, L.T., Malim, M.H., Kim, J.H., Hauber, J., Duc Dodon, M., Le, S.Y., Maizel, J.V., Cullen, B.R., Greene, W.C. Genes Dev. (1989) [Pubmed]
  19. High human T cell lymphotropic virus type 1 (HTLV-1)-specific precursor cytotoxic T lymphocyte frequencies in patients with HTLV-1-associated neurological disease. Elovaara, I., Koenig, S., Brewah, A.Y., Woods, R.M., Lehky, T., Jacobson, S. J. Exp. Med. (1993) [Pubmed]
  20. Configuration and expression of the T cell receptor beta chain gene in human T-lymphotrophic virus I-infected cells. Jarrett, R.F., Mitsuya, H., Mann, D.L., Cossman, J., Broder, S., Reitz, M.S. J. Exp. Med. (1986) [Pubmed]
  21. Rat lymphoid cell lines producing human T cell leukemia virus. II. Constitutive expression of rat interleukin 2 receptor. Yodoi, J., Okada, M., Tagaya, Y., Teshigawara, K., Fukui, K., Ishida, N., Ikuta, K., Maeda, M., Honjo, T., Osawa, H. J. Exp. Med. (1985) [Pubmed]
  22. Detection of human T lymphotrophic virus type I (HTLV-I) proviral DNA and analysis of T cell receptor V beta CDR3 sequences in spinal cord lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis. Hara, H., Morita, M., Iwaki, T., Hatae, T., Itoyama, Y., Kitamoto, T., Akizuki, S., Goto, I., Watanabe, T. J. Exp. Med. (1994) [Pubmed]
  23. Human T cell leukemia/lymphoma virus I infection and subsequent cloning of normal human B cells. Direct responsiveness of cloned cells to recombinant interleukin 2 by differentiation in the absence of enhanced proliferation. Tomita, S., Ambrus, J.L., Volkman, D.J., Longo, D.L., Mitsuya, H., Reitz, M.S., Fauci, A.S. J. Exp. Med. (1985) [Pubmed]
  24. Serum reactivity to human T-cell leukaemia/lymphoma virus type I proteins in patients with large granular lymphocytic leukaemia. Starkebaum, G., Loughran, T.P., Kalyanaraman, V.S., Kadin, M.E., Kidd, P.G., Singer, J.W., Ruscetti, F.W. Lancet (1987) [Pubmed]
  25. Signal transducer and activator of transcription-3 (STAT3) is constitutively activated in normal, self-renewing B-1 cells but only inducibly expressed in conventional B lymphocytes. Karras, J.G., Wang, Z., Huo, L., Howard, R.G., Frank, D.A., Rothstein, T.L. J. Exp. Med. (1997) [Pubmed]
  26. Interleukin-2 receptor (Tac antigen) expressed on adult T cell leukemia cells. Uchiyama, T., Hori, T., Tsudo, M., Wano, Y., Umadome, H., Tamori, S., Yodoi, J., Maeda, M., Sawami, H., Uchino, H. J. Clin. Invest. (1985) [Pubmed]
  27. HTLV-1 Tax protein interacts with cyclin-dependent kinase inhibitor p16INK4A and counteracts its inhibitory activity towards CDK4. Suzuki, T., Kitao, S., Matsushime, H., Yoshida, M. EMBO J. (1996) [Pubmed]
  28. Activation of the IL-2 gene promoter by HTLV-I tax involves induction of NF-AT complexes bound to the CD28-responsive element. Good, L., Maggirwar, S.B., Sun, S.C. EMBO J. (1996) [Pubmed]
  29. Oligodendrocyte-specific expression and autoantigenicity of transaldolase in multiple sclerosis. Banki, K., Colombo, E., Sia, F., Halladay, D., Mattson, D.H., Tatum, A.H., Massa, P.T., Phillips, P.E., Perl, A. J. Exp. Med. (1994) [Pubmed]
  30. A rat model of human T lymphocyte virus type I (HTLV-I) infection. 1. Humoral antibody response, provirus integration, and HTLV-I-associated myelopathy/tropical spastic paraparesis-like myelopathy in seronegative HTLV-I carrier rats. Ishiguro, N., Abe, M., Seto, K., Sakurai, H., Ikeda, H., Wakisaka, A., Togashi, T., Tateno, M., Yoshiki, T. J. Exp. Med. (1992) [Pubmed]
  31. Factors secreted by human T lymphotropic virus type I (HTLV-I)-infected cells can enhance or inhibit replication of HIV-1 in HTLV-I-uninfected cells: implications for in vivo coinfection with HTLV-I and HIV-1. Moriuchi, H., Moriuchi, M., Fauci, A.S. J. Exp. Med. (1998) [Pubmed]
  32. Detection of human T-lymphotropic virus-like particles in cultures of peripheral blood lymphocytes from patients with mycosis fungoides. Zucker-Franklin, D., Coutavas, E.E., Rush, M.G., Zouzias, D.C. Proc. Natl. Acad. Sci. U.S.A. (1991) [Pubmed]
  33. Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector. Grassmann, R., Dengler, C., Müller-Fleckenstein, I., Fleckenstein, B., McGuire, K., Dokhelar, M.C., Sodroski, J.G., Haseltine, W.A. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
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