1887

Abstract

Human Jurkat T cells containing a stably integrated human T cell leukaemia virus type 1 (HTLV-1) long terminal repeat (LTR) reporter gene construct were used to study the role of calcium-dependent cellular activation pathways in LTR trans-activation. Treatment of these cells with the calcium ionophore ionomycin resulted in a reduced basal response of the LTR and reduced responses to 12--tetradecanoylphorbol-13-acetate- and Tax-mediated trans-activation. This effect was also observed for virus production in the HTLV-1-producing T cell line MT-2. Experiments designed to determine the events underlying this inhibition, using inhibitors of calcium-related events, revealed that the ionomycin- induced repression of the LTR was alleviated in all cases by cyclosporin A. This compound was also effective in preventing the ionomycin-induced reduction in virus production in MT-2 cells. These results suggest a role for calcium-related events in the down-regulation of HTLV-1 expression.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-75-7-1623
1994-07-01
2021-10-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/75/7/JV0750071623.html?itemId=/content/journal/jgv/10.1099/0022-1317-75-7-1623&mimeType=html&fmt=ahah

References

  1. Albrecht H., Shakhov A. N., Jongeneel C. V. 1992; Trans activation of the tumor necrosis factor alpha promoter by the human T-cell leukemia virus type I taxi protein. Journal of Virology 66:6191–6193
    [Google Scholar]
  2. Alcover A., Ramarli D., Richardson N. E., Chang H. C., Reinherz E. L. 1987; Functional and molecular aspects of human T lymphocyte activation via T3-Ti and T11 pathways. Immunological Reviews 95:5–36
    [Google Scholar]
  3. Arya S. 1988; Human immunodeficiency virus type-2 gene expression: two enhancers and their activation by T-cell activators. AIDS Research and Human Retroviruses 4:175–178
    [Google Scholar]
  4. Blumberg P. M. 1991; Complexities of the protein kinase C pathway. Molecular Carcinogenesis 4:339–344
    [Google Scholar]
  5. Bosselut R., Duvall J. F., Gegonne A., Bailly M., Hemar A., Brady J., Ghysdael J. 1990; The product of the c-ets-1 protooncogene and the related Ets2 protein act as transcriptional activators of human T cell leukemia virus HTLV-1. EMBO Journal 9:3137–3144
    [Google Scholar]
  6. Cacalano N. A., Chen B.-X., Cleveland W. L., Erlanger B. F. 1992; Evidence for a functional receptor for cyclosporin A on the surface of lymphocytes. Proceedings of the National Academy of Sciences, U.S.A 89:4353–4357
    [Google Scholar]
  7. Chen I. S. Y., Slamon D. J., Rosenblatt J. D., Shah N. P., Quan S. G., Wachsman W. 1985; The X gene is essential for HTLV-1 replication. Science 229:54–57
    [Google Scholar]
  8. Clark N. M., Smith M. J., Hilfinger J. M., Markovitz D. M. 1993; Activation of the human T-cell leukemia virus type I enhancer is mediated by binding sites for elf-1 and the pets factor. Journal of Virology 67:5522–5528
    [Google Scholar]
  9. Clevers H., Alarcon B., Wileman T., Terhorst C. 1988; The T-cell receptor/CD3 complex: a dynamic protein ensemble. Annual Review of Immunology 6:629–662
    [Google Scholar]
  10. Clipstone N. A., Crabtree G. R. 1992; Identification of cal-cineurin as a key signallingenzyme in T-lymphocyte activation. Nature; London: 357695–697
    [Google Scholar]
  11. Copeland K. F. T., Haaksma A. G. M., Derse D., Goudsmit J., Heeney J. L. 1993; Cytochemical analysis of HTLV-1 regulated β-galactosidase expression using a novel integrated cell system. Journal of Virological Methods 45:161–167
    [Google Scholar]
  12. Depper J. M., Leonard W. J., Kronke M., Waldman T. A., Greene W. C. 1984; Augmented T cell growth factor receptor expression in HTLV-1-infected human leukemic T cells. Journal of Immunology 133:1691–1695
    [Google Scholar]
  13. Derse D., Martarano L. 1990; Construction of a recombinant bovine leukemia virus vector for analysis of virus infectivity. Journal of Virology 4:401–405
    [Google Scholar]
  14. Ejima E., Rosenblatt J. D., Massari M., Quan E., Stephens C., Rosen C., Prager D. 1993; Cell-type-specific transactivation of the parathyroid hormone-related protein gene promoter by the human T-cell leukemia virus type 1 (HTLV-I) tax and HTLV-II tax proteins. Blood 81:1017–1024
    [Google Scholar]
  15. Emmel E. A., Verweij C. L., Durand D. B., Higgins K. M., Lacy E., Crabtree G. R. 1989; Cyclosporin A specifically inhibits function of nuclear proteins involved in T cell activation. Science 226:1439–1441
    [Google Scholar]
  16. Fiering S., Northrop J. P., Nolan G. P., Mattila P. S., Crabtree G. R., Herzenberg L. A. 1990; Single cell assay of a transcription factor reveals a threshold in transcription activated by signals emanating from the T-cell antigen receptor. Genes and Development 4:1823–1834
    [Google Scholar]
  17. Finkel T. H., Mcduffie M., Kappler J. W., Marrack P., Cambier J. C. 1987; Both immature and mature T cells mobilize Ca2+ in response to antigen receptor crosslinking. Nature; London: 330179–181
    [Google Scholar]
  18. Fisher C. L., Ghysdael J., Cambier J. C. 1991; Ligation of membrane Ig leads to calcium-mediated phosphorylation of the proto-oncogene product, Ets-1. Journal of Immunology 146:1743–1749
    [Google Scholar]
  19. Flanagan W. M., Corthesy B., Bram B., Crabtree G. R. 1991; Nuclear association of a T-cell transcription factor blocked by FK-506 and cyclosporin A. Nature; London: 352803–807
    [Google Scholar]
  20. Fox H. B., Gutman P. D., Dave H. P. G., Cao S. X., Mittelman M., Berg P. E., Schechter A. N. 1989; Trans-activation of human globin genes by HTLV-I tax. Blood 74:2749–2754
    [Google Scholar]
  21. Franchini G., Wong-Staal F., Gallo R. C. 1984; Human T-cell leukemia virus (HTLV-1) transcripts in fresh and cultured cells of patients with adult T-cell leukemia. Proceedings of the National Academy of Sciences, U.S.A 81:6207–6211
    [Google Scholar]
  22. Fuji M., Sassone-Corsi P., Verma I. M. 1988; c-fos promoter transactivation by the tax I protein of human T-cell leukemia virus type I. Proceedings of the National Academy of Sciences, U.S.A 85:8526–8530
    [Google Scholar]
  23. Gardner P. 1989; Calcium and T lymphocyte activation. Cell 59:15–20
    [Google Scholar]
  24. Gelfand E. W., Mills G. B., Cheung R. K., Lee J. W. W., Grinstein S. 1987; Transmembrane ion fluxes during activation of human T lymphocytes: role of Ca2+, Na+/H+ exchange and phospholipid turnover. Immunological Reviews 95:59–87
    [Google Scholar]
  25. Gessain A., Barin F., Vernant J. C. 1985; Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet ii:407–410
    [Google Scholar]
  26. Gessain A., Louie A., Gout O., Gallo R. C., Franchini G. 1991; Human T-cell leukemia-lymphoma virus type 1 (HTLV-1) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis/HTLV-1 associated myelopathy. Journal of Virology 65:1628–1633
    [Google Scholar]
  27. Gootenberg J. E., Rescetti F. W., Mier J. M., Gazdar A., Gallo R. C. 1981; Human cutaneous T cell lymphoma and leukemia cell lines produce and respond to T cell growth factor. Journal of Experimental Medicine 154:1403–1418
    [Google Scholar]
  28. Gruters R. A., Otto S., Al B. J. M., Verhoeven A. J., Verweij C. L., Van Lier R. A. W., Miedema F. 1991; Nonmitogenic T-cell activation signals are sufficient for induction of human immunodeficiency virus transcription. European Journal of Immunology 21:167–172
    [Google Scholar]
  29. Gunter K. C., Irving S. G., Zipfel P. F., Siebenlist U., Kelly K. 1989; Cyclosporin A-mediated inhibition of mitogen-inducible gene transcription is specific for the mitogenic stimulus and cell type. Journal of Immunology 142:3286–3291
    [Google Scholar]
  30. Hattori T., Uchiyama T., Toibana T., Takatsuki K., Ichino H. 1981; Surface phenotype of Japanese adult T-cell leukemia cells characterized by monoclonal antibodies. Blood 58:645–647
    [Google Scholar]
  31. Hinuma Y., Nagata K., Hanaoka M., Matsumoto T., Kinoshita K., Shirakawa S., Miyoshi I. 1981; Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera. Proceedings of the National Academy of Sciences, U.S.A 78:6476–6480
    [Google Scholar]
  32. Hoshino H., Simoyama M., Sugimura T. 1983; Detection of lymphocytes producing a human retrovirus associated with adult T-cell leukemia by syncytia induction assay. Proceedings of the National Academy of Sciences, U.S.A 80:7337–7341
    [Google Scholar]
  33. Itoyama Y., Minato S., Kira J., Goto I., Sato H., Okochi K., Yamamoto N. 1988; Spontaneous proliferation of peripheral blood lymphocytes increases in patients with HTLV-1-associated myelopathy. Neurology 38:1302–1307
    [Google Scholar]
  34. Jacobson S., Zaninovic V., Mora C., Rodgers-Johnson P., Sheremata W. S., Gibbs C. J., Gadjusek D. C., Mcfarlin D. E. 1988; Immunological findings in neurological disease associated with antibodies to HTLV-1: activated lymphocytes in tropical spastic paraparesis. Annals of Neurology 23:S196–S200
    [Google Scholar]
  35. Kashanchi F., Duvall J. F., Lindholm P. F., Radonovich M. F., Brady J. N. 1993; Sequences downstream of the RNA initiation site regulate human T-cell leukemia virus type I basal gene expression. Journal of Virology 67:2894–2902
    [Google Scholar]
  36. Kinoshita T., Shimoyama M., Tobinai K., Ito M., Ito S., Tajima K., Shimotono K., Sugimura T. 1989; Detection of mRNA for the tax1/rex1 gene of human T-cell leukemia virus type 1 in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction. Proceedings of the National Academy of Sciences, U.S.A 86:5620–5624
    [Google Scholar]
  37. Kay J. E., Doe S. E. A., Benzie C. R. 1989; The mechanism of action of the immunosuppressive drug FK-506. Cellular Immunology 124:175–181
    [Google Scholar]
  38. Koyano-Nakagawa N., Nishida J., Arai N., Arai K., Yokota T. 1993; Reconstitution of the functional granulocyte macrophage colony stimulating factor promoter: evidence for distinct activation mechanisms that mediate the response to phorbol ester/calcium and human T cell leukemia virus type I tax signals. International Immunology 5:345–352
    [Google Scholar]
  39. Leung K., Nabel G. J. 1988; HTLV-I transactivation induces interleukin-2 receptor expression through an NFkB-like factor. Nature; London: 333776–778
    [Google Scholar]
  40. Lilienbaum A., Ducdodon M., Alexander C., Gazzolo L., Paulin D. 1990; Effect of human T-cell leukemia virus type I tax protein on activation of the human vimentin gene. Journal of Virology 64:256–263
    [Google Scholar]
  41. Lin C. S., Coltz R. C., Siekierka J. J., Sigal N. H. 1991; FK-506 and cyclosporin A inhibit highly similar signal transduction pathways in human T lymphocytes. Cellular Immunology 133:269–284
    [Google Scholar]
  42. Lindholm P. F., Reid R. L., Brady J. N. 1992; Extracellular taxi protein stimulates tumor necrosis factor-β and immunoglobulin kappa light chain expression in lymphoid cells. Journal of Virology 66:1294–1302
    [Google Scholar]
  43. Mccaffrey P. G., Perrino B. A., Soderling T. R., Rao A. 1993; NF-ATp, a T lymphocyte DNA-binding protein that is a target for calcineurin and immunosuppressive drugs. Journal of Biological Chemistry 268:3747–3752
    [Google Scholar]
  44. Mccauley L. K., Rosol T. J., Merryman J. I., Capen C. C. 1992; Parathyroid hormone-related protein binding to human T-cell lymphotropic virus type I-infected lymphocytes. Endocrinology 130:300–306
    [Google Scholar]
  45. Mattila P. S., Ullman K. S., Fiering S., Mccutcheon M., Crabtree G. R., Herzenberg L. A. 1990; The actions of cyclosporin A and FK506 suggest a novel step in the activation of T lymphocytes. EMBO Journal 9:4425–4433
    [Google Scholar]
  46. Minta A., Kao J. P. Y., Tsien R. Y. 1989; Fluorescent indicators for cytosoloic calcium based on rhodamine and fluorescein chromophores. Journal of Biological Chemistry 264:8171–8178
    [Google Scholar]
  47. Osame M., Usuku K., Izumo S., Ijichi N., Amitini H., Igata A., Matsumoto M., Tara M. 1986; HTLV-1 associated myelopathy, a new clinical entity. Lancet i:1031–1032
    [Google Scholar]
  48. Poiesz B. J., Ruscetti F. W., Gazdar A. F., Bunn P. A., Minna J. D., Gallo R. C. 1980; Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma. Proceedings of the National Academy of Sciences, U.S.A 77:7415–7419
    [Google Scholar]
  49. Popovic M., Lange-Wantzin G., Sarin P. S., Mann D., Gallo R. C. 1983; Transformation of human umbilical cord blood T cells by human T cell leukemia/lymphoma virus. Proceedings of the National Academy of Sciences, U.S.A 80:5402–5406
    [Google Scholar]
  50. Radonovich M., Jeang K.-T. 1989; Activation of the human T-cell leukemia virus long terminal repeat by 12-O-tetra- decanoylphorbol-13-acetate and by tax (p40x) occurs through similar but functionally distinct target sequences. Journal of Virology 63:2987–2994
    [Google Scholar]
  51. Randak C., Brabletz T., Hergenrother M., Sobotta I., Serfling E. 1990; Cyclosporin A suppresses the expression of the interleukin 2 gene by inhibiting the binding of lymphocyte-specific factors to the IL-2 enhancer. EMBO Journal 9:2529–2536
    [Google Scholar]
  52. Siekevitz M., Feinberg M. M., Holbrook N., Wong-Staal F., Greene W. C. 1987a; Activation of interleukin 2 and interleukin 2 receptor (Tac) promoter expression by the trans-activator (tat) gene product of human T-cell leukemia virus, type I. Proceedings of the National Academy of Sciences, U.S.A 84:5389–5393
    [Google Scholar]
  53. Siekevitz M., Josephs S. F., Dukovich M., Peffer N., Wong-Staal F., Greene W. C. 1987b; Activation of the HIV-1 LTR by T cell mitogens and trans-activator protein of HTLV-1. Science 238:1575–1578
    [Google Scholar]
  54. Sodroski J. G., Rosen C. A., Goh W. C., Haseltine W. A. 1985; A transcriptional activator protein encoded by the X-lor region of the human T-cell leukemia virus. Science 228:1430–1434
    [Google Scholar]
  55. Sugamura K., Fujii M., Kannagi M., Sakitini M., Takeuchi M., Hinuma Y. 1984; Cell surface phenotypes and expression of viral antigens of various human cell lines carrying human T-cell leukemia virus. International Journal of Cancer 34:221–228
    [Google Scholar]
  56. Tendler C. L., Greenberg S. J., Blattner W. A., Manns A., Murphy E., Fleisher T., Hanchard B., Morgan O., Burton J. D., Nelson D. L., Waldmann T. A. 1990; Transactivation of interleukin 2 and its receptor induces immune activation in human T- cell lymphotropic virus type I-associated myelopathy: pathogenic implications and a rationale for therapy. Proceedings of the National Academy of Sciences, U.S.A 87:5218–5222
    [Google Scholar]
  57. Ullman K. S., Northrop J. P., Admon A., Crabtree G. R. 1993; Jun family members are controlled by a calcium-regulated, cyclosporin A-sensitive signaling pathway in activated T lymphocytes. Genes and Development 1:188–196
    [Google Scholar]
  58. Vandenberghe P. A., Ceuppens J. L. 1990; Flow cytometric measurement of cytoplasmic free calcium in human peripheral blood T lymphocytes with Fluo-3, a new fluorescent calcium indicator. Journal of Immunological Methods 127:197–205
    [Google Scholar]
  59. Varmus H. 1988; Regulation of HIV and HTLV gene expression. Genes and Development 2:1055–1062
    [Google Scholar]
  60. Yodoi J., Uchiyama T., Maeda M. 1983; T-cell growth factor receptor in adult T-cell leukemia. Blood 62:509–511
    [Google Scholar]
  61. Yoshida M., Miyoshi I., Hinuma Y. 1982; Isolation and characterization of retrovirus from cell lines of human and adult T-cell leukemia and its implication in the disease. Proceedings of the National Academy of Sciences, U.S.A 79:2031–2035
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-75-7-1623
Loading
/content/journal/jgv/10.1099/0022-1317-75-7-1623
Loading

Data & Media loading...

Most cited this month Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error