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T-Cell Control by Human T-Cell Leukemia/Lymphoma Virus Type 1

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Abstract

Human T-cell leukemia/lymphoma virus type 1 (HTLV-1) causes neoplastic transformation of human T-cells in a small number of infected individuals several years from infection. Collective evidence from in vitro studies indicates that several viral proteins act in concert to increase the responsiveness of T-cells to extracellular stimulation, modulate proapoptotic and antiapoptotic gene signals, enhance T-cell survival, and avoid immune recognition of the infected T-cells. The virus promotes T-cell proliferation by usurping several signaling pathways central to immune T-cell function, such as antigen stimulation and receptor-ligand interaction, suggesting that extracellular signals are important for HTLV-1 oncogenesis. Environmental factors such as chronic antigen stimulation may therefore be of importance, as also suggested by epidemiological data. Thus genetic and environmental factors together with the virus contribute to disease development. This review focuses on current knowledge of the mechanisms regulating HTLV-1 replication and the T-cell pathways that are usurped by viral proteins to induce and maintain clonal proliferation of infected T-cells. The relevance of these laboratory findings is related to clonal T-cell proliferation and adult T-cell leukemia/lymphoma development in vivo.

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References

  1. Gallo RC. The first human retrovirus.Sci Am. 1986;255:88–98.

    Article  PubMed  CAS  Google Scholar 

  2. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC. 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;77:7415–7419.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. 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;79:2031–2035.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  4. Miyoshi I, Kubonishi I, Yoshimoto S, et al. 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;294:770–771.

    Article  PubMed  CAS  Google Scholar 

  5. Blattner WA, Kalyanaraman VS, Robert-Guroff M, et al. The human type-C retrovirus, HTLV, in Blacks from the Caribbean region, and relationship to adult T-cell leukemia/lymphoma.Int J Cancer. 1982;30:257–264.

    Article  PubMed  CAS  Google Scholar 

  6. Catovsky D, Greaves MF, Rose M, et al. Adult T-cell lymphomaleukaemia in blacks from the West Indies.Lancet. 1982;1:639–643.

    Article  PubMed  CAS  Google Scholar 

  7. Hinuma Y, Nagata K, Hanaoka M, et al. 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;78:6476–6480.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Robert-Guroff M, Ruscetti FW, Posner LE, Poiesz BJ, Gallo RC. Detection of the human T cell lymphoma virus p19 in cells of some patients with cutaneous T cell lymphoma and leukemia using a monoclonal antibody.J Exp Med. 1981;154:1957–1964.

    Article  PubMed  CAS  Google Scholar 

  9. Takatsuki K, Uchiayama T, Sagawa K, Yodoi J. Adult T-cell leukemia in Japan. In: Seno S, Takaku F, Irino S, eds.Topics in Hematology. Amsterdam: Excerpta Medicia; 1977:73.

    Google Scholar 

  10. Gessain A, Barin F, Vernant JC, et al. Antibodies to human T-lymphotropic virus type I in patients with tropical spastic paraparesis.Lancet. 1985;2:407–410.

    Article  PubMed  CAS  Google Scholar 

  11. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A. HTLV-I associated myelopathy, a new clinical entity.Lancet. 1986;1:1031–1032.

    Article  PubMed  CAS  Google Scholar 

  12. Rodgers-Johnson P, Gajdusek DC, Morgan OS, Zaninavic V, Sarin PS, Graham DS. HTLV-I and HTLV-III antibodies and tropical spastic paraparesis.Lancet. 1985;2:1247–1249.

    Article  PubMed  CAS  Google Scholar 

  13. Bangham CR. The immune response to HTLV-I.Curr Opin Immunol. 2000;12:397–402.

    Article  PubMed  CAS  Google Scholar 

  14. Hollsberg P, Hafler DA.What is the pathogenesis of human T-cell lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis?Ann Neurol. 1995;37:143–145.

    Article  PubMed  CAS  Google Scholar 

  15. Jacobson S, Shida H, McFarlin DE, Fauci AS, Koenig S. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease.Nature. 1990;348:245–248.

    Article  PubMed  CAS  Google Scholar 

  16. Jacobson S. Immunopathogenesis of human T cell lymphotropic virus type I-associated neurologic disease.J Infect Dis. 2002;186(suppl 2):S187-S192.

    Article  PubMed  Google Scholar 

  17. Osame M. Pathological mechanisms of human T-cell lymphotropic virus type I-associated myelopathy (HAM/TSP).J Neurovirol. 2002;8:359–364.

    Article  PubMed  CAS  Google Scholar 

  18. Blattner WA.Epidemiology of HTLV-I and Associated Diseases. New York: Raven; 1990.

    Google Scholar 

  19. Murphy EL, Hanchard B, Figueroa JP, et al. Modeling the risk of adult T-cell leukemia/lymphoma in persons infected with human T-lymphotropic virus type I.Int J Cancer. 1989;43:250–253.

    Article  PubMed  CAS  Google Scholar 

  20. Yamaguchi K, Takatsuki K. Adult T cell leukaemia-lymphoma.Baillieres Clin Haematol. 1993;6:899–915.

    Article  PubMed  CAS  Google Scholar 

  21. de The G, Bomford R. An HTLV-I vaccine: why, how, for whom?AIDS Res Hum Retroviruses. 1993;9:381–386.

    Article  PubMed  Google Scholar 

  22. Tajima K, Kuroishi T. Estimation of rate of incidence of ATL among ATLV (HTLV-I) carriers in Kyushu, Japan.Jpn J Clin Oncol. 1985;15:423–430.

    PubMed  CAS  Google Scholar 

  23. Wong-Staal F, Hahn B, Manzari V, et al. A survey of human leukaemias for sequences of a human retrovirus.Nature. 1983;302:626–628.

    Article  PubMed  CAS  Google Scholar 

  24. Yoshida M, Seiki M, Yamaguchi K, Takatsuki K. Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease.Proc Natl Acad Sci U S A. 1984;81:2534–2537.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Takatsuki K, Yamaguchi K, Kawano F, et al. Clinical diversity in adult T-cell leukemia-lymphoma.Cancer Res. 1985;45:4644s-4645s.

    PubMed  CAS  Google Scholar 

  26. Yamaguchi K, Nishimura H, Kawano F, et al. A proposal for smoldering adult T-cell leukemia: diversity in clinical pictures of adult T-cell leukemia.Jpn J Clin Oncol. 1983;13:189–199.

    PubMed  Google Scholar 

  27. Seiki M, Hattori S, Kirayama Y, Yoshida M. Human T-cell leukemia/lymphotropic virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA.Proc Natl Acad Sci U S A. 1983;80:3618–3622.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  28. Fields BN, Knipe DM, Howley PM.Fields Virology. Philadelphia: Lippincott-Raven; 1996.

    Google Scholar 

  29. Bertola F, Manigand C, Picard P, Goetz M, Schmitter JM, Precigoux G. N-Terminal domain of HTLV-I integrase: complexation and conformational studies of the zinc finger.J Pept Sci. 2001;7:588–597.

    Article  PubMed  CAS  Google Scholar 

  30. Ha JJ, Gaul DA, Mariani VL, Ding YS, Ikeda RA, Shuker SB. HTLV-I protease cleavage of P19/24 substrates is not dependent on NaCl concentration.Bioorg Chem. 2002;30:138–144.

    Article  PubMed  CAS  Google Scholar 

  31. Heidecker G, Hill S, Lloyd PA, Derse D. A novel protease processing site in the transframe protein of human T-cell leukemia virus type 1 PR76(gag-pro) defines the N terminus of RT.J Virol. 2002;76:13101–13105.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Kobayashi M, Ohi Y, Asano T, et al. Purification and characterization of human T-cell leukemia virus type I protease produced inEscherichia coli.FEBS Lett. 1991;293:106–110.

    Article  PubMed  CAS  Google Scholar 

  33. Le Blanc I, Prevost MC, Dokhelar MC, Rosenberg AR. The PPPY motif of human T-cell leukemia virus type 1 Gag protein is required early in the budding process.J Virol. 2002;76:10024–10029.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  34. Mariani VL, Beckham SS. Identification of the RT-RH/IN cleavage site of HTLV-I.Biochem Biophys Res Commun. 2003;300:268–270.

    Article  PubMed  CAS  Google Scholar 

  35. Muller B, Krausslich HG. Characterization of human T-cell leukemia virus type I integrase expressed inEscherichia coli.Eur J Biochem. 1999;259:79–87.

    Article  PubMed  CAS  Google Scholar 

  36. Trentin B, Rebeyrotte N, Mamoun RZ. Human T-cell leukemia virus type 1 reverse transcriptase (RT) originates from the pro and pol open reading frames and requires the presence of RT-RNase H (RH) and RT-RH-integrase proteins for its activity.J Virol. 1998;72:6504–6510.

    PubMed  PubMed Central  CAS  Google Scholar 

  37. Ciminale V, Pavlakis GN, Derse D, Cunningham CP, Felber BK. Complex splicing in the human T-cell leukemia virus (HTLV) family of retroviruses: novel mRNAs and proteins produced by HTLV-I.J Virol. 1992;66:1737–1745.

    PubMed  PubMed Central  CAS  Google Scholar 

  38. Koralnik I, Gessain A, Klotman ME, Lo Monico A, Berneman ZN, Franchini G. Protein isoforms encoded by the pX region of the human T-cell leukemia/lymphotropic virus type I.Proc Natl Acad Sci U S A. 1992;89:8813–8817.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Koralnik IJ, Fullen J, Franchini G. The p12I, p13II, and p30II proteins encoded by human T-cell leukemia/lymphotropic virus type I open reading frames I and II are localized in three different cellular compartments.J Virol. 1993;67:2360–2366.

    PubMed  PubMed Central  CAS  Google Scholar 

  40. Franchini G, Mulloy JC, Koralnik IJ, et al. The human T-cell leukemia/lymphotropic virus type I p12I protein cooperates with the E5 oncoprotein of bovine papillomavirus in cell transformation and binds the 16-kilodalton subunit of the vacuolar H+ ATPase.J Virol. 1993;67:7701–7704.

    PubMed  PubMed Central  CAS  Google Scholar 

  41. Ding W, Albrecht B, Kelley RE, et al. Human T-cell lymphotropic virus type 1 p12(I) expression increases cytoplasmic calcium to enhance the activation of nuclear factor of activated T cells.J Virol. 2002;76:10374–10382.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  42. Albrecht B, D’souza CD, Ding W, Tridandapani S, Coggeshall KM, Lairmore MD. Activation of nuclear factor of activated T cells by human T-lymphotropic virus type 1 accessory protein p12(I).J Virol. 2002;76:3493–3501.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  43. Johnson JM, Nicot C, Fullen J, et al. Free major histocompatibility complex class I heavy chain is preferentially targeted for degradation by human T-cell leukemia/lymphotropic virus type 1 p12(I) protein.J Virol. 2001;75:6086–6094.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  44. Mulloy JC, Kislyakova T, Cereseto A, et al. Human T-cell lymphotropic/ leukemia virus type 1 Tax abrogates p53-induced cell cycle arrest and apoptosis through its CREB/ATF functional domain.J Virol. 1998;72:8852–8860.

    PubMed  PubMed Central  CAS  Google Scholar 

  45. Nicot C, Mulloy JC, Ferrari MG, et al. HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells.Blood. 2001;98:823–829.

    Article  PubMed  CAS  Google Scholar 

  46. Nicot C, Dundr M, Johnson JM, Fukumoto R, Misteli T, Franchini G. A novel negative regulator of HTLV-1 replication. Unpublished manuscript.

  47. Zhang W, Nisbet JW, Bartoe JT, Ding W, Lairmore MD. Human T-lymphotropic virus type 1 p30(II) functions as a transcription factor and differentially modulates CREB-responsive promoters.J Virol. 2000;74:11270–11277.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  48. Zhang W, Nisbet JW, Albrecht B, et al. Human T-lymphotropic virus type 1 p30(II) regulates gene transcription by binding CREB binding protein/p300.J Virol. 2001;75:9885–9895.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Berneman ZN, Gartenhaus RB, Reitz MS Jr, et al. Expression of alternatively spliced human T-lymphotropic virus type I (HTLV-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;89:3005–3009.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  50. Ciminale V, Zotti L, D’Agostino DM, et al. Mitochondrial targeting of the p13II protein coded by the x-II ORF of human T-cell leukemia/lymphotropic virus type I (HTLV-I).Oncogene. 1999;18:4505–4514.

    Article  PubMed  CAS  Google Scholar 

  51. D’Agostino DM, Ranzato L, Arrigoni G, et al. Mitochondrial alterations induced by the p13II protein of human T-cell leukemia virus type 1: critical role of arginine residues.J Biol Chem. 2002;277:34424–34433.

    Article  PubMed  Google Scholar 

  52. Aldovini A, De Rossi A, Feinberg MB, Wong-Staal F, Franchini G. Molecular analysis of a deletion mutant provirus of type I human T-cell lymphotropic virus: evidence for a doubly spliced x-lor mRNA.Proc Natl Acad Sci U S A. 1986;83:38–42.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Seiki M, Hikikoshi A, Taniguchi T, Yoshida M. Expression of the pX gene of HTLV-I: general splicing mechanism in the HTLV family.Science. 1985;228:1532–1534.

    Article  PubMed  CAS  Google Scholar 

  54. Wachsman W, Golde DW, Temple PA, Orr EC, Clark SC, Chen IS. HTLV x-gene product: requirement for the env methionine initiation codon.Science. 1985;228:1534–1537.

    Article  PubMed  CAS  Google Scholar 

  55. Felber BK. Regulation of mRNA expression in HIV-1 and other retroviruses. In: Harford JB, Morris DR, eds.mRNA Metabolism and Post-Transcriptional Gene Regulation. New York: Wiley-Liss; 1997:323–340.

    Google Scholar 

  56. Orita S, Saiga A, Takagi S, et al. A novel alternatively spliced viral mRNA transcribed in cells infected with human T cell leukemia virus type 1 is mainly responsible for expressing p21X protein.FEBS Lett. 1991;295:127–134.

    Article  PubMed  CAS  Google Scholar 

  57. Gaudray G, Gachon F, Basbous J, Biard-Piechaczyk M, Devaux C, Mesnard JM. The complementary strand of the human T-cell leukemia virus type 1 RNA genome encodes a bZIP transcription factor that down-regulates viral transcription.J Virol. 2002;76:12813–12822.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  58. Larocca D, Chao LA, Seto MH, Brunck TK. Human T-cell leukemia virus minus strand transcription in infected T-cells.Biochem Biophys Res Commun. 1989;163:1006–1013.

    Article  PubMed  CAS  Google Scholar 

  59. Ballard DW, Dohnlein E, Lowenthal JW, Wano Y, Franza BR, Greene WC. HTLV-I tax induces cellular proteins that activate the kappa B element in the IL-2 receptor alpha gene.Science. 1988;241:1652–1655.

    Article  PubMed  CAS  Google Scholar 

  60. Hiscott J, Kwon H, Genin P. Hostile takeovers: viral appropriation of the NF-kappaB pathway.J Clin Invest. 2001;107:143–151.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Jeang KT. Functional activities of the human T-cell leukemia virus type I Tax oncoprotein: cellular signaling through NF-kappa B.Cytokine Growth Factor Rev. 2001;12:207–217.

    Article  PubMed  CAS  Google Scholar 

  62. Yoshida M, Suzuki T. HTLV-I oncoprotein Tax and cellular transcription factors.Curr Top Microbiol Immunol. 1995;193:79–89.

    PubMed  CAS  Google Scholar 

  63. Marriott SJ, Lemoine FJ, Jeang KT. Damaged DNA and miscounted chromosomes: human T cell leukemia virus type I tax oncoprotein and genetic lesions in transformed cells.J Biomed Sci. 2002;9:292–298.

    Article  PubMed  CAS  Google Scholar 

  64. Ding W, Albrecht B, Luo R, et al. Endoplasmic reticulum and cis-Golgi localization of human T-lymphotropic virus type 1 p12(I): association with calreticulin and calnexin.J Virol. 2001;75:7672–7682.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  65. Albrecht B, Collins ND, Burniston MT, et al. Human T-lymphotropic virus type 1 open reading frame I p12(I) is required for efficient viral infectivity in primary lymphocytes.J Virol. 2000;74:9828–9835.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  66. Derse D, Mikovits J, Ruscetti F. X-I and X-II open reading frames of HTLV-I are not required for virus replication or for immortalization of primary T-cells in vitro.Virology. 1997;237:123–128.

    Article  PubMed  CAS  Google Scholar 

  67. Robek MD, Wong FH, Ratner L. Human T-cell leukemia virus type 1 pX-I and pX-II open reading frames are dispensable for the immortalization of primary lymphocytes.J Virol. 1998;72:4458–4462.

    PubMed  PubMed Central  CAS  Google Scholar 

  68. Collins ND, Newbound GC, Albrecht B, Beard JL, Ratner L, Lairmore MD. Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo.Blood. 1998;91:4701–4707.

    PubMed  CAS  Google Scholar 

  69. Martins ML, Soares BC, Ribas JG, et al. Frequency of p12K and p12R alleles of HTLV Type 1 in HAM/TSP patients and in asymptomatic HTLV type 1 carriers.AIDS Res Hum Retroviruses. 2002;18:899–902.

    Article  PubMed  CAS  Google Scholar 

  70. Trovato R, Mulloy JC, Johnson JM, Takemoto S, de Oliveira MP, Franchini G. A lysine-to-arginine change found in natural alleles of the HTLV-I p12I protein greatly influences its stability.J Virol. 1999;73:6460–6467.

    PubMed  PubMed Central  CAS  Google Scholar 

  71. Franchini G. Molecular mechanisms of human T-cell leukemia/ lymphotropic virus type I infection.Blood. 1995;86:3619–3639.

    PubMed  CAS  Google Scholar 

  72. Feller SM, Ren R, Hanafusa H, Baltimore D. SH2 and SH3 domains as molecular adhesives: the interactions of Crk and Abl.Trends Biochem Sci. 1994;19:453–458.

    Article  PubMed  CAS  Google Scholar 

  73. Mayer BJ. SH3 domains: complexity in moderation.J Cell Sci. 2001;114:1253–1263.

    PubMed  CAS  Google Scholar 

  74. Koralnik I, Mulloy JC, Andresson T, Fullen J, Franchini G. Mapping of the intermolecular association of the human T-cell leukemia/ lymphotropic virus type 1 p12I and the vacuolar H+ATPase 16 kDa subunit protein.J Gen Virol. 1995;76:1909–1916.

    Article  PubMed  CAS  Google Scholar 

  75. Stevens TH, Forgac M. Structure, function and regulation of the vacuolar (H+)-ATPase.Annu Rev Cell Dev Biol. 1997;13:779–808.

    Article  PubMed  CAS  Google Scholar 

  76. Mulloy JC, Crowley RW, Fullen J, Leonard WJ, Franchini G. The human T-cell leukemia/lymphotropic virus type I p12I protein binds the interleukin-2 receptor β and βc chains and affects their expression on the cell surface.J Virol. 1996;70:3599–3605.

    PubMed  PubMed Central  CAS  Google Scholar 

  77. Lewis RS. Calcium signaling mechanisms in T lymphocytes.Annu Rev Immunol. 2001;19:497–521.

    Article  PubMed  CAS  Google Scholar 

  78. Rusnak F, Mertz P. Calcineurin: form and function.Physiol Rev. 2000;80:1483–1521.

    Article  PubMed  CAS  Google Scholar 

  79. Bonifacino JS, Klausner RD. Degradation of proteins retained in the endoplasmic reticulum. In: Ciechanover A, Schwartz AL, eds.Cellular Proteolytic Systems. New York:Wiley-Liss; 1994:137.

    Google Scholar 

  80. Plemper RK, Wolf DH. Retrograde protein translocation: ERADication of secretory proteins in health and disease.Trends Biochem Sci. 1999;24:266–270.

    Article  PubMed  CAS  Google Scholar 

  81. Nagai M, Usuku K, Matsumoto W, et al. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP.J Neurovirol. 1998;4:586–593.

    Article  PubMed  CAS  Google Scholar 

  82. D’Agostino DM, Zotti L, Ferro T, et al. Expression and functional properties of proteins encoded in the x-II ORF of HTLV-I.Virus Res. 2001;78:35–43.

    Article  PubMed  Google Scholar 

  83. Bartoe JT, Albrecht B, Collins ND, et al. Functional role of pX open reading frame II of human T-lymphotropic virus type 1 in maintenance of viral loads in vivo.J Virol. 2000;74:1094–1100.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  84. D’Agostino DM, Ciminale V, Zotti L, Rosato A, Chieco-Bianchi L. The human T-cell lymphotropic virus type 1 Tof protein contains a bipartite nuclear localization signal that is able to functionally replace the amino-terminal domain of Rex.J Virol. 1997;71:75–83.

    PubMed  PubMed Central  Google Scholar 

  85. Hemelaar J, Bex F, Booth B, Cerundolo V, McMichael A, Daenke S. Human T-cell leukemia virus type 1 Tax protein binds to assembled nuclear proteasomes and enhances their proteolytic activity.J Virol. 2001;75:11106–11115.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  86. Desagher S, Martinou JC. Mitochondria as the central control point of apoptosis.Trends Cell Biol. 2000;10:369–377.

    Article  PubMed  CAS  Google Scholar 

  87. Rojo G, Chamorro M, Salas ML, Vinuela E, Cuezva JM, Salas J. Migration of mitochondria to viral assembly sites in African swine fever virus-infected cells.J Virol. 1998;72:7583–7588.

    PubMed  PubMed Central  CAS  Google Scholar 

  88. Lefebvre L, Vanderplasschen A, Ciminale V, et al. Oncoviral bovine leukemia virus G4 and human T-cell leukemia virus type 1 p13(II) accessory proteins interact with farnesyl pyrophosphate synthetase.J Virol. 2002;76:1400–1414.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  89. Rao KN. The significance of the cholesterol biosynthetic pathway in cell growth and carcinogenesis [review].Anticancer Res. 1995;15:309–314.

    PubMed  CAS  Google Scholar 

  90. 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;82:8359–8363.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  91. 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;60:394–399.

    PubMed  PubMed Central  CAS  Google Scholar 

  92. Furukawa K, Furukawa K, Shiku H. Alternatively spliced mRNA of the pX region of human T-lymphotropic virus type 1 proviral genome.FEBS Lett. 1991;295:141–145.

    Article  PubMed  CAS  Google Scholar 

  93. Kubota S, Hatanaka M, Pomerantz RJ. Nucleo-cytoplasmic redistribution of the HTLV-I Rex protein: alterations by coexpression of the HTLV-I p21x protein.Virology. 1996;220:502–507.

    Article  PubMed  CAS  Google Scholar 

  94. Orita S, Takagi S, Saiga A, et al. Human T cell leukaemia virus type 1 p21X mRNA: constitutive expression in peripheral blood mononuclear cells of patients with adult T cell leukaemia.J Gen Virol. 1992;73:2283–2289.

    Article  PubMed  CAS  Google Scholar 

  95. 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;7:519–523.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  96. 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;209:187–190.

    Article  PubMed  CAS  Google Scholar 

  97. Inoue J, Itoh M, Akizawa T, Toyoshima H, Yoshida M. HTLV-1 Rex protein accumulates unspliced RNA in the nucleus as well as in cytoplasm.Oncogene. 1991;6:1753–1757.

    PubMed  CAS  Google Scholar 

  98. Nosaka T, Siomi H, Adachi Y, et al. 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;86:9798–9802.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  99. Ohta M, Nyunoya H, Tanaka H, Okamoto T, Akagi T, Shimotohno K. Identification of a cis-regulatory element involved in accumulation of human T-cell leukemia virus type II genomic mRNA.J Virol. 1988;62:4445–4451.

    PubMed  PubMed Central  CAS  Google Scholar 

  100. Siomi H, Shida H, Nam SH, 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;55:197–209.

    Article  PubMed  CAS  Google Scholar 

  101. Smith MR, Greene WC. Type I human T cell leukemia virus tax protein transforms rat fibroblasts through the cyclic adenosine monophosphate response element binding protein/activating transcription factor pathway.J Clin Invest. 1991;88:1038–1042.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  102. Ballaun C, Farrington GK, Dobrovnik M, Rusche J, Hauber J, Bohnlein E. Functional analysis of human T-cell leukemia virus type I rex-response element: direct RNA binding of Rex protein correlates with in vivo activity.J Virol. 1991;65:4408–4413.

    PubMed  PubMed Central  CAS  Google Scholar 

  103. Bar-Shira A, Panet A, Honigman A. An RNA secondary structure juxtaposes two remote genetic signals for human T-cell leukemia virus type I RNA 3′-end processing.J Virol. 1991;65:5165–5173.

    PubMed  PubMed Central  CAS  Google Scholar 

  104. Hanly SM, Rimsky LT, Malim MH, et al. Comparative analysis of the HTLV-I Rex and HIV-1 Rev trans-regulatory proteins and their RNA response elements.Genes Dev. 1989;3:1534–1544.

    Article  PubMed  CAS  Google Scholar 

  105. Seiki M, Inoue J, Hidaka M, Yoshida M. Two cis-acting elements responsible for posttranscriptional trans-regulation of gene expression of human T-cell leukemia virus type I.Proc Natl Acad Sci U S A. 1988;85:7124–7128.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  106. Unge T, Solomin L, Mellini M, Derse D, Felber BK, Pavlakis GN. The Rex regulatory protein of human T-cell lymphotropic virus type I binds specifically to its target site within the viral RNA.Proc Natl Acad Sci U S A. 1991;88:7145–7149.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  107. Yoshida M, Seiki M. Recent advances in the molecular biology of HTLV-1: trans-activation of viral and cellular genes.Annu Rev Immunol. 1987;5:541–559.

    Article  PubMed  CAS  Google Scholar 

  108. Adachi Y, Copeland TD, Takahashi C, et al. Phosphorylation of the Rex protein of human T-cell leukemia virus type I.J Biol Chem. 1992;267:21977–21981.

    PubMed  CAS  Google Scholar 

  109. Grone M, Koch C, Grassmann R. The HTLV-1 Rex protein induces nuclear accumulation of unspliced viral RNA by avoiding intron excision and degradation.Virology. 1996;218:316–325.

    Article  PubMed  CAS  Google Scholar 

  110. Kanamori H, Suzuki N, Siomi H, et al. HTLV-1 p27rex stabilizes human interleukin-2 receptor alpha chain mRNA.EMBO J. 1990;9:4161–4166.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  111. McGuire KL, Curtiss VE, Larson EL, Haseltine WA. Influence of human T-cell leukemia virus type I tax and rex on interleukin-2 gene expression.J Virol. 1993;67:1590–1599.

    PubMed  PubMed Central  CAS  Google Scholar 

  112. Sodroski JG, Rosen CA, Haseltine WA. Transacting transcriptional activation of the long terminal repeat of human T lymphotropic viruses in infected cells.Science. 1984;225:381–385.

    Article  PubMed  CAS  Google Scholar 

  113. Cann AJ, Rosenblatt JD, Wachsman W, Shah NP, Chen IS. Identification of the gene responsible for human T-cell leukaemia virus transcriptional regulation.Nature. 1985;318:571–574.

    Article  PubMed  CAS  Google Scholar 

  114. Felber BK, Paskalis H, Wong-Staal F, Pavlakis GN. The pX protein of HTLV-I is a transcriptional activator of its long terminal repeats.Science. 1985;229:675–679.

    Article  PubMed  CAS  Google Scholar 

  115. Sodroski J, Rosen C, Goh WC, Haseltine W. A transcriptional activator protein encoded by the x-lor region of the human T-cell leukemia virus.Science. 1985;228:1430–1434.

    Article  PubMed  CAS  Google Scholar 

  116. Sodroski JG, Goh WC, Rosen CA, et al. trans-Activation of the human T-cell leukemia virus long terminal repeat correlates with expression of the x-lor protein.J Virol. 1985;55:831–835.

    PubMed  PubMed Central  CAS  Google Scholar 

  117. Stevenson M. Molecular mechanisms for the regulation of HIV replication, persistence and latency.AIDS. 1997;11(suppl A):S25-S33.

    PubMed  Google Scholar 

  118. Kronke M, Leonard WJ, Depper JM, Greene WC. Deregulation of interleukin-2 receptor gene expression in HTLV-I-induced adult T-cell leukemia.Science. 1985;228:1215–1217.

    Article  PubMed  CAS  Google Scholar 

  119. Lando Z, Sarin P, Megson M, et al. Association of human T-cell leukaemia/lymphoma virus with the Tac antigen marker for the human T-cell growth factor receptor.Nature. 1983;305:733–736.

    Article  PubMed  CAS  Google Scholar 

  120. Greene WC, Leonard WJ, Wano Y, et al. Trans-activator gene of HTLV-II induces IL-2 receptor and IL-2 cellular gene expression.Science. 1986;232:877–880.

    Article  PubMed  CAS  Google Scholar 

  121. Cross SL, Feinberg MB, Wolf JB, Holbrook NJ, Wong-Staal F, Leonard WJ. Regulation of the human interleukin-2 receptor alpha chain promoter: activation of a nonfunctional promoter by the transactivator gene of HTLV-I.Cell. 1987;49:47–56.

    Article  PubMed  CAS  Google Scholar 

  122. Inoue J, Seiki M, Taniguchi T, Tsuru S, Yoshida M. Induction of interleukin 2 receptor gene expression by p40x encoded by human T-cell leukemia virus type 1.EMBO J. 1986;5:2883–2888.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  123. Leung K, Nabel GJ. HTLV-1 transactivator induces interleukin-2 receptor expression through an NF-kappa B-like factor.Nature. 1988;333:776–778.

    Article  PubMed  CAS  Google Scholar 

  124. Maruyama M, Shibuya H, Harada H, et al. Evidence for aberrant activation of the interleukin-2 autocrine loop by HTLV-1-encoded p40x and T3/Ti complex triggering.Cell. 1987;48:343–350.

    Article  PubMed  CAS  Google Scholar 

  125. Ruben S, Poteat H, Tan TH, et al. Cellular transcription factors and regulation of IL-2 receptor gene expression by HTLV-I tax gene product.Science. 1988;241:89–92.

    Article  PubMed  CAS  Google Scholar 

  126. Siekevitz M, Feinberg MB, Holbrook N, Wong-Staal F, Greene WC. 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.Proc Natl Acad Sci U S A. 1987;84:5389–5393.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Baeuerle PA, Baltimore D. NF-kappa B: ten years after.Cell. 1996;87:13–20.

    Article  PubMed  CAS  Google Scholar 

  128. Alexandre C, Charnay P, Verrier B.Transactivation of Krox-20 and Krox-24 promoters by the HTLV-1 Tax protein through common regulatory elements.Oncogene. 1991;6:1851–1857.

    PubMed  CAS  Google Scholar 

  129. Fujii M, Tsuchiya H, Chuhjo T, Akizawa T, Seiki M. Interaction of HTLV-1 Tax1 with p67SRF causes the aberrant induction of cellular immediate early genes through CArG boxes.Genes Dev. 1992;6:2066–2076.

    Article  PubMed  CAS  Google Scholar 

  130. Goodman RH, Smolik S. CBP/p300 in cell growth, transformation, and development.Genes Dev. 2000;14:1553–1577.

    PubMed  CAS  Google Scholar 

  131. Yoshida M. Multiple viral strategies of HTLV-1 for dysregulation of cell growth control.Annu Rev Immunol. 2001;19:475–496.

    Article  PubMed  CAS  Google Scholar 

  132. Fujii M, Tsuchiya H, Chuhjo T, Minamino T, Miyamoto K, Seiki M. Serum response factor has functional roles both in indirect binding to the CArG box and in the transcriptional activation function of human T-cell leukemia virus type I Tax.J Virol. 1994;68:7275–7283.

    PubMed  PubMed Central  CAS  Google Scholar 

  133. Herdegen T, Leah JD. Inducible and constitutive transcription factors in the mammalian nervous system: control of gene expression by Jun, Fos and Krox, and CREB/ATF proteins.Brain Res Brain Res Rev. 1998;28:370–490.

    Article  PubMed  CAS  Google Scholar 

  134. Suzuki T, Hirai H, Fujisawa J, Fujita K, Yoshida M. A trans-activator Tax of human T-cell leukemia virus type 1 binds to NF-kappa B p50 and serum response factor (SRF) and associates with enhancer DNAs of the NF-kappa B site and CArG box.Oncogene. 1993;8:2391–2397.

    PubMed  CAS  Google Scholar 

  135. Tsuchiya H, Fujii M, Niki T, Tokuhara M, Matsui M, Seiki M. Human T-cell leukemia virus type 1 Tax activates transcription of the human fra-1 gene through multiple cis elements responsive to transmembrane signals.J Virol. 1993;67:7001–7007.

    PubMed  PubMed Central  CAS  Google Scholar 

  136. Shuh M, Derse D. Ternary complex factors and cofactors are essential for human T-cell leukemia virus type 1 tax transactivation of the serum response element.J Virol. 2000;74:11394–11397.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  137. Armstrong AP, Franklin AA, Uittenbogaard MN, Giebler HA, Nyborg JK. Pleiotropic effect of the human T-cell leukemia virus Tax protein on the DNA binding activity of eukaryotic transcription factors.Proc Natl Acad Sci U S A. 1993;90:7303–7307.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  138. Jin G, Howe PH. Regulation of clusterin gene expression by transforming growth factor beta.J Biol Chem. 1997;272:26620–26626.

    Article  PubMed  CAS  Google Scholar 

  139. Mori N, Fujii M, Iwai K, et al. Constitutive activation of transcription factor AP-1 in primary adult T-cell leukemia cells.Blood. 2000;95:3915–3921.

    PubMed  CAS  Google Scholar 

  140. Jeang KT,Widen SG, Semmes OJ, IV, Wilson SH. HTLV-I transactivator protein, tax, is a trans-repressor of the human betapolymerase gene.Science. 1990;247:1082–1084.

    Article  PubMed  CAS  Google Scholar 

  141. Uittenbogaard MN, Armstrong AP, Chiaramello A, Nyborg JK. Human T-cell leukemia virus type I Tax protein represses gene expression through the basic helix-loop-helix family of transcription factors.J Biol Chem. 1994;269:22466–22469.

    PubMed  CAS  Google Scholar 

  142. Lemasson I, Robert-Hebmann V, Hamaia S, Duc DM, Gazzolo L, Devaux C. Transrepression of lck gene expression by human T-cell leukemia virus type 1-encoded p40tax.J Virol. 1997;71:1975–1983.

    PubMed  PubMed Central  CAS  Google Scholar 

  143. Uittenbogaard MN, Giebler HA, Reisman D, Nyborg JK. Transcriptional repression of p53 by human T-cell leukemia virus type I Tax protein.J Biol Chem. 1995;270:28503–28506.

    Article  PubMed  CAS  Google Scholar 

  144. Suzuki T, Hirai H, Murakami T, Yoshida M. Tax protein of HTLV-1 destabilizes the complexes of NF-kappa B and I kappa B-alpha and induces nuclear translocation of NF-kappa B for transcriptional activation.Oncogene. 1995;10:1199–1207.

    PubMed  CAS  Google Scholar 

  145. Suzuki T, Uchida-Toita M, Yoshida M. Tax protein of HTLV-1 inhibits CBP/p300-mediated transcription by interfering with recruitment of CBP/p300 onto DNA element of E-box or p53 binding site.Oncogene. 1999;18:4137–4143.

    Article  PubMed  CAS  Google Scholar 

  146. Brauweiler A, Garrus JE, Reed JC, Nyborg JK. Repression of bax gene expression by the HTLV-1 Tax protein: implications for suppression of apoptosis in virally infected cells.Virology. 1997;231:135–140.

    Article  PubMed  CAS  Google Scholar 

  147. Nicot C, Mahieux R, Opavsky R, et al. HTLV-I Tax transrepresses the human c-Myb promoter independently of its interaction with CBP or p300.Oncogene. 2000;19:2155–2164.

    Article  PubMed  CAS  Google Scholar 

  148. Nicot C, Opavsky R, Mahieux R, et al. Tax oncoprotein transrepresses the endogenous B-myb promoter activity in human T cells.AIDS Res Hum Retroviruses. 2000;16:1629–1632.

    Article  PubMed  CAS  Google Scholar 

  149. Nicot C, Mahieux R, Pise-Masison C, et al. Human T-cell lymphotropic virus type 1 Tax represses c-Myb-dependent transcription through activation of the NF-kappaB pathway and modulation of coactivator usage.Mol Cell Biol. 2001;21:7391–7402.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  150. Arnulf B, Villemain A, Nicot C, et al. Human T-cell lymphotropic virus oncoprotein Tax represses TGF-beta 1 signaling in human T cells via c-Jun activation: a potential mechanism of HTLV-I leukemogenesis.Blood. 2002;100:4129–4138.

    Article  PubMed  CAS  Google Scholar 

  151. Lee DK, Kim BC, Brady JN, Jeang KT, Kim SJ. Human T-cell lymphotropic virus type 1 tax inhibits transforming growth factor-beta signaling by blocking the association of Smad proteins with Smadbinding element.J Biol Chem. 2002;277:33766–33775.

    Article  PubMed  CAS  Google Scholar 

  152. Mori N, Morishita M, Tsukazaki T, et al. Human T-cell leukemia virus type I oncoprotein Tax represses Smad-dependent transforming growth factor beta signaling through interaction with CREB-binding protein/p300.Blood. 2001;97:2137–2144.

    Article  PubMed  CAS  Google Scholar 

  153. Azimi N, Brown K, Bamford RN, Tagaya Y, Siebenlist U, Waldmann TA. Human T cell lymphotropic virus type I Tax protein trans-activates interleukin 15 gene transcription through an NFkappaB site.Proc Natl Acad Sci U S A. 1998;95:2452–2457.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  154. Azimi N, Nagai M, Jacobson S, Waldmann TA. IL-15 plays a major role in the persistence of Tax-specific CD8 cells in HAM/TSP patients.Proc Natl Acad Sci U S A. 2001;98:14559–14564.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  155. Mariner JM, Lantz V, Waldmann TA, Azimi N. Human T cell lymphotropic virus type I Tax activates IL-15Ralpha gene expression through an NF-kappaB site.J Immunol. 2001;166:2602–2609.

    Article  PubMed  CAS  Google Scholar 

  156. Kirken RA, Erwin RA, Wang L, Wang Y, Rui H, Farrar WL. Functional uncoupling of the Janus kinase 3-Stat5 pathway in malignant growth of human T cell leukemia virus type 1-transformed human T cells.J Immunol. 2000;165:5097–5104.

    Article  PubMed  CAS  Google Scholar 

  157. Li-Weber M, Giaisi M, Chlichlia K, Khazaie K, Krammer PH. Human T cell leukemia virus type I Tax enhances IL-4 gene expression in T cells.Eur J Immunol. 2001;31:2623–2632.

    Article  PubMed  CAS  Google Scholar 

  158. Mori N, Prager D. Transactivation of the interleukin-1alpha promoter by human T-cell leukemia virus type I and type II Tax proteins.Blood. 1996;87:3410–3417.

    PubMed  CAS  Google Scholar 

  159. Mori N, Prager D. Interleukin-10 gene expression and adult T-cell leukemia.Leuk Lymphoma. 1998;29:239–248.

    Article  PubMed  CAS  Google Scholar 

  160. Mori N, Mukaida N, Ballard DW, Matsushima K, Yamamoto N. Human T-cell leukemia virus type I Tax transactivates human interleukin 8 gene through acting concurrently on AP-1 and nuclear factor-kappaB-like sites.Cancer Res. 1998;58:3993–4000.

    PubMed  CAS  Google Scholar 

  161. Yamashita I, Katamine S, Moriuchi R, et al. Transactivation of the human interleukin-6 gene by human T-lymphotropic virus type 1 Tax protein.Blood. 1994;84:1573–1578.

    PubMed  CAS  Google Scholar 

  162. Chieco-Bianchi L, Saggioro D, Del Mistro A, Montaldo A, Majone F, Levis AG. Chromosome damage induced in cord blood T-lymphocytes infected in vitro by HTLV-I.Leukemia. 1988;2:223S-232S.

    PubMed  CAS  Google Scholar 

  163. Markham PD, Salahuddin SZ, Kalyanaraman VS, Popovic M, Sarin P, Gallo RC. Infection and transformation of fresh human umbilical cord blood cells by multiple sources of human T-cell leukemia-lymphoma virus (HTLV).Int J Cancer. 1983;31:413–420.

    Article  PubMed  CAS  Google Scholar 

  164. Popovic M, Lange-Wantzin G, Sarin PS, Mann D, Gallo RC. Transformation of human umbilical cord blood T-cells by human T-cell leukemia/lymphoma virus.Proc Natl Acad Sci U S A. 1983;80:5402–5406.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  165. Reid RL, Lindholm PF, Mireskandari A, Dittmer J, Brady JN. Stabilization of wild type p53 in human T-lymphocytes transformed by HTLV-I.Oncogene. 1993;8:3029–3036.

    PubMed  CAS  Google Scholar 

  166. Yamato K, Oka T, Hiroi M, et al. Aberrant expression of the p53 tumor suppressor gene in adult T-cell leukemia and HTLV-Iinfected cells.Jpn J Cancer Res. 1993;84:4–8.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  167. Cereseto A, Diella F, Mulloy JC, et al. p53 functional impairment and high p21waf1/cip1 expression in human T-cell lymphotropic/ leukemia virus type I-transformed T-cells.Blood. 1996;88:1551–1560.

    PubMed  CAS  Google Scholar 

  168. Akagi T, Ono H, Shimotohno K. Expression of cell-cycle regulatory genes in HTLV-I infected T-cell lines: possible involvement of Tax1 in the altered expression of cyclin D2, p18Ink4 and p21waf1/ cip1/sdi1.Oncogene. 1996;12:1645–1652.

    PubMed  CAS  Google Scholar 

  169. Schmitt I, Rosin O, Rohwer P, Gossen M, Grassmann R. Stimulation of cyclin-dependent kinase activity and G1- to S-phase transition in human lymphocytes by the human T-cell leukemia/lymphotropic virus type 1 Tax protein.J Virol. 1998;72:633–640.

    PubMed  PubMed Central  CAS  Google Scholar 

  170. Pise-Masison CA, Choi KS, Radonovich M, Dittmer J, Kim SJ, Brady JN. Inhibition of p53 transactivation function by the human T-cell lymphotropic virus type 1 Tax protein.J Virol. 1998;72:1165–1170.

    PubMed  PubMed Central  CAS  Google Scholar 

  171. Akagi T, Ono H, Tsuchida N, Shimotohno K. Aberrant expression and function of p53 in T-cells immortalized by HTLV-I Tax 1.FEBS Lett. 1997;406:263–266.

    Article  PubMed  CAS  Google Scholar 

  172. Pise-Masison CA, Radonovich M, Sakaguchi K, Appella E, Brady JN. Phosphorylation of p53: a novel pathway for p53 inactivation in human T-cell lymphotropic virus type 1-transformed cells.J Virol. 1998;72:6348–6355.

    PubMed  PubMed Central  CAS  Google Scholar 

  173. Pise-Masison CA, Mahieux R, Radonovich MF, Jiang H, Brady JN. Human T-lymphotropic virus type I Tax protein utilizes distinct pathways for p53 inhibition that are cell type-dependent.J Biol Chem. 2001;276:200–205.

    Article  PubMed  CAS  Google Scholar 

  174. Van PL, Yim KW, Jin DY, Dapolito G, Kurimasa A, Jeang KT. Genetic evidence of a role for ATM in functional interaction between human T-cell leukemia virus type 1 Tax and p53.J Virol. 2001;75:396–407.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  175. Chaudhry S, Freebern WJ, Smith JL, Butscher WG, Haggerty CM, Gardner K. Cross-regulation of T cell growth factor expression by p53 and the tax oncogene.J Immunol. 2002;169:6767–6778.

    Article  PubMed  CAS  Google Scholar 

  176. Pise-Masison CA, Mahieux R, Jiang H, et al. Inactivation of p53 by human T-cell lymphotropic virus type 1 Tax requires activation of the NF-kappaB pathway and is dependent on p53 phosphorylation.Mol Cell Biol. 2000;20:3377–3386.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  177. Ariumi Y, Kaida A, Lin JY, et al. HTLV-1 tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration.Oncogene. 2000;19:1491–1499.

    Article  PubMed  CAS  Google Scholar 

  178. Livengood JA, Scoggin KE, Van Orden K, et al. p53 Transcriptional activity is mediated through the SRC1-interacting domain of CBP/p300.J Biol Chem. 2002;277:9054–9061.

    Article  PubMed  CAS  Google Scholar 

  179. Van Orden K, Giebler HA, Lemasson I, Gonzales M, Nyborg JK. Binding of p53 to the KIX domain of CREB binding protein: a potential link to human T-cell leukemia virus, type I-associated leukemogenesis.J Biol Chem. 1999;274:26321–26328.

    Article  PubMed  Google Scholar 

  180. Kaida A, Ariumi Y, Ueda Y, et al. Functional impairment of p73 and p51, the p53-related proteins, by the human T-cell leukemia virus type 1 Tax oncoprotein.Oncogene. 2000;19:827–830.

    Article  PubMed  CAS  Google Scholar 

  181. Lemasson I, Nyborg JK. Human T-cell leukemia virus type I tax repression of p73beta is mediated through competition for the C/H1 domain of CBP.J Biol Chem. 2001;276:15720–15727.

    Article  PubMed  CAS  Google Scholar 

  182. Lu H, Pise-Masison CA, Fletcher TM, et al. Acetylation of nucleosomal histones by p300 facilitates transcription from tax-responsive human T-cell leukemia virus type 1 chromatin template.Mol Cell Biol. 2002;22:4450–4462.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  183. Cheng H, Cenciarelli C, Shao Z, et al. Human T cell leukemia virus type 1 Tax associates with a molecular chaperone complex containing hTid-1 and Hsp70.Curr Biol. 2001;11:1771–1775.

    Article  PubMed  CAS  Google Scholar 

  184. Schilling B, De Medina T, Syken J, Vidal M, Munger K. A novel human DnaJ protein, hTid-1, a homolog of theDrosophila tumor suppressor protein Tid56, can interact with the human papillomavirus type 16 E7 oncoprotein.Virology. 1998;247:74–85.

    Article  PubMed  CAS  Google Scholar 

  185. Lemoine FJ, Marriott SJ. Accelerated G(1) phase progression induced by the human T cell leukemia virus type I (HTLV-I) Tax oncoprotein.J Biol Chem. 2001;276:31851–31857.

    Article  PubMed  CAS  Google Scholar 

  186. Hinds PW, Weinberg RA. Tumor suppressor genes.Curr Opin Genet Dev. 1994;4:135–141.

    Article  PubMed  CAS  Google Scholar 

  187. Nevins JR. E2F: a link between the Rb tumor suppressor protein and viral oncoproteins.Science. 1992;258:424–429.

    Article  PubMed  CAS  Google Scholar 

  188. Morgan DO. Principles of CDK regulation.Nature. 1995;374:131–134.

    Article  PubMed  CAS  Google Scholar 

  189. Peter M, Herskowitz I. Joining the complex: cyclin-dependent kinase inhibitory proteins and the cell cycle.Cell. 1994;79:181–184.

    Article  PubMed  CAS  Google Scholar 

  190. Sherr CJ, Roberts JM. Inhibitors of mammalian G1 cyclin-dependent kinases.Genes Dev. 1995;9:1149–1163.

    Article  PubMed  CAS  Google Scholar 

  191. Harper JW, Adami GR, Wei N, Keyomarsi K, Elledge SJ. The p21 Cdk-interacting protein Cip1 is a potent inhibitor of G1 cyclindependent kinases.Cell. 1993;75:805–816.

    Article  PubMed  CAS  Google Scholar 

  192. Cereseto A, Washington-Parks R, Rivadeneira E, Franchini G. Limiting amounts of p27kip1 correlates with constitutive activation of cyclin E-CDK2 complex in HTLV-I-transformed T-cells.Oncogene. 1999;18:2441–2450.

    Article  PubMed  CAS  Google Scholar 

  193. el-Deiry WS, Tokino T, Velculescu VE, et al. WAF1, a potential mediator of p53 tumor suppression.Cell. 1993;75:817–825.

    Article  PubMed  CAS  Google Scholar 

  194. Haller K, Ruckes T, Schmitt I, Saul D, Derow E, Grassmann R. Taxdependent stimulation of G1 phase-specific cyclin-dependent kinases and increased expression of signal transduction genes characterize HTLV type 1-transformed T cells.AIDS Res Hum Retroviruses. 2000;16:1683–1688.

    Article  PubMed  CAS  Google Scholar 

  195. Low KG, Dorner LF, Fernando DB, Grossman J, Jeang KT, Comb MJ. Human T-cell leukemia virus type 1 tax releases cell cycle arrest induced by p16INK4a.J Virol. 1997;71:1956–1962.

    PubMed  PubMed Central  CAS  Google Scholar 

  196. Suzuki T, Kitao S, Matsushime H, Yoshida M. HTLV-I Tax protein interacts with cyclin-dependent kinase inhibitor p16ink4a and counteracts its inhibitory activity towards CDK4.EMBO J. 1996;15:1607–1614.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  197. Suzuki T, Narita T, Uchida-Toita M, Yoshida M. Down-regulation of the INK4 family of cyclin-dependent kinase inhibitors by tax protein of HTLV-1 through two distinct mechanisms.Virology. 1999;259:384–391.

    Article  PubMed  CAS  Google Scholar 

  198. Mori N, Fujii M, Hinz M, et al. Activation of cyclin D1 and D2 promoters by human T-cell leukemia virus type I tax protein is associated with IL-2-independent growth of T cells.Int J Cancer. 2002;99:378–385.

    Article  PubMed  CAS  Google Scholar 

  199. Santiago F, Clark E, Chong S, et al. Transcriptional up-regulation of the cyclin D2 gene and acquisition of new cyclin-dependent kinase partners in human T-cell leukemia virus type 1-infected cells.J Virol. 1999;73:9917–9927.

    PubMed  PubMed Central  CAS  Google Scholar 

  200. Huang Y, Ohtani K, Iwanaga R, Matsumura Y, Nakamura M. Direct trans-activation of the human cyclin D2 gene by the oncogene product Tax of human T-cell leukemia virus type I.Oncogene. 2001;20:1094–1102.

    Article  PubMed  CAS  Google Scholar 

  201. Mori N, Fujii M, Cheng G, et al. Human T-cell leukemia virus type I tax protein induces the expression of anti-apoptotic gene Bcl-xL in human T-cells through nuclear factor-kappaB and c-AMP responsive element binding protein pathways.Virus Genes. 2001;22:279–287.

    Article  PubMed  CAS  Google Scholar 

  202. Lemasson I, Thebault S, Sardet C, Devaux C, Mesnard JM. Activation of E2F-mediated transcription by human T-cell leukemia virus type I Tax protein in a p16(INK4A)-negative T-cell line.J Biol Chem. 1998;273:23598–23604.

    Article  PubMed  CAS  Google Scholar 

  203. Macleod KF, Sherry N, Hannon G, et al. p53 dependent and independent expression of p21 during cell growth, differentiation, and DNA damage.Genes Dev. 1995;9:935–944.

    Article  PubMed  CAS  Google Scholar 

  204. Zhang H, Hannon J, Beach D. p21-containing cyclin kinases exist in both active and inactive states.Genes Dev. 1994;8:1750–1758.

    Article  PubMed  CAS  Google Scholar 

  205. de La Fuente C, Deng L, Santiago F, Arce L, Wang L, Kashanchi F. Gene expression array of HTLV type 1-infected T cells: up-regulation of transcription factors and cell cycle genes.AIDS Res Hum Retroviruses. 2000;16:1695–1700.

    Article  Google Scholar 

  206. Iwanaga R, Ohtani K, Hayashi T, Nakamura M. Molecular mechanism of cell cycle progression induced by the oncogene product Tax of human T-cell leukemia virus type I.Oncogene. 2001;20:2055–2067.

    Article  PubMed  CAS  Google Scholar 

  207. Kao SY, Marriott SJ. Disruption of nucleotide excision repair by the human T-cell leukemia virus type 1 Tax protein.J Virol. 1999;73:4299–4304.

    PubMed  PubMed Central  CAS  Google Scholar 

  208. Kao SY, Lemoine FJ, Marriott SJ. Suppression of DNA repair by human T cell leukemia virus type 1 Tax is rescued by a functional p53 signaling pathway.J Biol Chem. 2000;275:35926–35931.

    Article  PubMed  CAS  Google Scholar 

  209. Lemoine FJ, Kao SY, Marriott SJ. Suppression of DNA repair by HTLV type 1 tax correlates with tax trans-activation of proliferating cell nuclear antigen gene expression.AIDS Res Hum Retroviruses. 2000;16:1623–1627.

    Article  PubMed  CAS  Google Scholar 

  210. Li Y, Jenkins CW, Nichols MA, Xiong Y. Cell cycle expression and p53 regulation of the cyclin-dependent kinase inhibitor p21.Oncogene. 1994;9:2261–2268.

    PubMed  CAS  Google Scholar 

  211. Mozzherin DJ, McConnell M, Jasko MV, et al. Proliferating cell nuclear antigen promotes misincorporation catalyzed by calf thymus DNA polymerase delta.J Biol Chem. 1996;271:31711–31717.

    Article  PubMed  CAS  Google Scholar 

  212. de La Fuente C, Santiago F, Chong SY, et al. Overexpression of p21(waf1) in human T-cell lymphotropic virus type 1-infected cells and its association with cyclin A/cdk2.J Virol. 2000;74:7270–7283.

    Article  PubMed Central  Google Scholar 

  213. Suzuki T, Uchida-Toita M, Andoh T, Yoshida M. HTLV-1 tax oncoprotein binds to DNA topoisomerase I and inhibits its catalytic activity.Virology. 2000;270:291–298.

    Article  PubMed  CAS  Google Scholar 

  214. Yoshida M, Suzuki T. HTLV type 1 Tax oncoprotein binds to DNA topoisomerase I and inhibits its catalytic activity.AIDS Res Hum Retroviruses. 2000;16:1639–1645.

    Article  PubMed  CAS  Google Scholar 

  215. Lemoine FJ, Marriott SJ. Genomic instability driven by the human T-cell leukemia virus type I (HTLV-I) oncoprotein,Tax.Oncogene. 2002;21:7230–7234.

    Article  PubMed  CAS  Google Scholar 

  216. Miyake H, Suzuki T, Hirai H, Yoshida M. Trans-activator Tax of human T-cell leukemia virus type 1 enhances mutation frequency of the cellular genome.Virology. 1999;253:155–161.

    Article  PubMed  CAS  Google Scholar 

  217. Poiesz BJ, Ruscetti FW, Mier JW, Woods AM, Gallo RC. 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;77:6815–6819.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  218. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. Adult T-cell leukemia: clinical and hematologic features of 16 cases.Blood. 1977;50:481–492.

    PubMed  CAS  Google Scholar 

  219. Fu DX, Kuo YL, Liu BY, Jeang KT, Giam CZ. Human T-lymphotropic virus type I tax activates I-kappa B kinase by inhibiting IKKgamma-associated serine/threonine protein phosphatase 2A.J Biol Chem. 2002;278:1487–1493.

    Article  PubMed  CAS  Google Scholar 

  220. Hardwick KG, Murray AW. Mad1p, a phosphoprotein component of the spindle assembly checkpoint in budding yeast.J Cell Biol. 1995;131:709–720.

    Article  PubMed  CAS  Google Scholar 

  221. Jin DY, Spencer F, Jeang KT. Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1.Cell. 1998;93:81–91.

    Article  PubMed  CAS  Google Scholar 

  222. Majone F, Semmes OJ, Jeang KT. Induction of micronuclei by HTLV-I Tax: a cellular assay for function.Virology. 1993;193:456–459.

    Article  PubMed  CAS  Google Scholar 

  223. Saggioro D, Majone F, Forino M, Turchetto L, Leszl A, Chieco-Bianchi L. Tax protein of human T-lymphotropic virus type I triggers DNA damage.Leuk Lymphoma. 1994;12:281–286.

    Article  PubMed  CAS  Google Scholar 

  224. Semmes OJ, Majone F, Cantemir C, Turchetto L, Hjelle B, Jeang KT. HTLV-I and HTLV-II Tax: differences in induction of micronuclei in cells and transcriptional activation of viral LTRs.Virology. 1996;217:373–379.

    Article  PubMed  CAS  Google Scholar 

  225. Campbell MS, Chan GK, Yen TJ. Mitotic checkpoint proteins HsMAD1 and HsMAD2 are associated with nuclear pore complexes in interphase.J Cell Sci. 2001;114:953–963.

    PubMed  CAS  Google Scholar 

  226. Cereseto A, Kislyakova T, Washington-Parks R, Franchini G. Differential response to genotoxic stress in immortalized or transformed HTLV-I-infected T-cells.J Gen Virol. 1999;80:1575–1581.

    Article  PubMed  CAS  Google Scholar 

  227. Chlichlia K, Busslinger M, Peter ME, et al. ICE-proteases mediate HTLV-I Tax-induced apoptotic T-cell death.Oncogene. 1997;14:2265–2272.

    Article  PubMed  CAS  Google Scholar 

  228. Hall AP, Irvine J, Blyth K, Cameron ER, Onions DE, Campbell ME. Tumours derived from HTLV-I tax transgenic mice are characterized by enhanced levels of apoptosis and oncogene expression.J Pathol. 1998;186:209–214.

    Article  PubMed  CAS  Google Scholar 

  229. Kao SY, Lemoine FJ, Mariott SJ. HTLV-1 Tax protein sensitizes cells to apoptotic cell death induced by DNA damaging agents.Oncogene. 2000;19:2240–2248.

    Article  PubMed  CAS  Google Scholar 

  230. Kao SY, Lemoine FJ, Marriott SJ. p53-Independent induction of apoptosis by the HTLV-I tax protein following UV irradiation.Virology. 2001;291:292–298.

    Article  PubMed  CAS  Google Scholar 

  231. Los M, Khazaie K, Schulze-Osthoff K, Baeuerle PA, Schirrmacher V, Chlichlia K. Human T cell leukemia virus-I (HTLV-I) Tax-mediated apoptosis in activated T cells requires an enhanced intracellular prooxidant state.J Immunol. 1998;161:3050–3055.

    PubMed  CAS  Google Scholar 

  232. Nicot C, Harrod R. Distinct p300-responsive mechanisms promote caspase-dependent apoptosis by human T-cell lymphotropic virus type 1.Mol Cell Biol. 2000;20:8580–8589.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  233. Yamada T, Yamaoka S, Goto T, Nakai M, Tsujimoto Y, Hatanaka M. The human T-cell leukemia virus type I Tax protein induces apoptosis which is blocked by the Bcl-2 protein.J Virol. 1994;68:3374–3379.

    PubMed  PubMed Central  CAS  Google Scholar 

  234. Arai M, Kannagi M, Matsuoka M, Sato T, Yamamoto N, Fujii M. Expression of FAP-1 (Fas-associated phosphatase) and resistance to Fas-mediated apoptosis in T cell lines derived from human T cell leukemia virus type 1-associated myelopathy/tropical spastic paraparesis patients.AIDS Res Hum Retroviruses. 1998;14:261–267.

    Article  PubMed  CAS  Google Scholar 

  235. Kasai T, Iwanaga Y, Iha H, Jeang KT. Prevalent loss of mitotic spindle checkpoint in adult T-cell leukemia confers resistance to microtubule inhibitors.J Biol Chem. 2002;277:5187–5193.

    Article  PubMed  CAS  Google Scholar 

  236. Kishi S, Saijyo S, Arai M, et al. Resistance to Fas-mediated apoptosis of peripheral T cells in human T lymphocyte virus type I (HTLV-I) transgenic mice with autoimmune arthropathy.J Exp Med. 1997;186:57–64.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  237. Nicot C, Astier-Gin T, Guillemain B. Activation of Bcl-2 expression in human endothelial cells chronically expressing the human T-cell lymphotropic virus type I.Virology. 1997;236:47–53.

    Article  PubMed  CAS  Google Scholar 

  238. Ruckes T, Saul D, Van Snick J, Hermine O, Grassmann R. Autocrine antiapoptotic stimulation of cultured adult T-cell leukemia cells by overexpression of the chemokine I-309.Blood. 2001;98:1150–1159.

    Article  PubMed  CAS  Google Scholar 

  239. Tsukahara T, Kannagi M, Ohashi T, et al. Induction of Bcl-x(L) expression by human T-cell leukemia virus type 1 Tax through NFkappaB in apoptosis-resistant T-cell transfectants with Tax.J Virol. 1999;73:7981–7987.

    PubMed  PubMed Central  CAS  Google Scholar 

  240. Yamada Y, Sugahara K, Tsuruda K, et al. Fas-resistance in ATL cell lines not associated with HTLV-I or FAP-1 production.Cancer Lett. 1999;147:215–219.

    Article  PubMed  CAS  Google Scholar 

  241. Nicot C, Mahieux R, Takemoto S, Franchini G. Bcl-XL is upregulated by HTLV type I and type II in vitro and in ex vivo ATLL samples.Blood. 2000;96:275–281.

    PubMed  CAS  Google Scholar 

  242. Rivera-Walsh I, Waterfield M, Xiao G, Fong A, Sun SC. NF-kappaB signaling pathway governs TRAIL gene expression and human T-cell leukemia virus-I Tax-induced T-cell death.J Biol Chem. 2001;276:40385–40388.

    Article  PubMed  CAS  Google Scholar 

  243. Rivera I, Harhaj EW, Sun SC. Involvement of NF-AT in type I human T-cell leukemia virus Tax-mediated Fas ligand promoter transactivation.J Biol Chem. 1998;273:22382–22388.

    Article  PubMed  CAS  Google Scholar 

  244. Rock KL, Gramm C, Rothstein L, et al. Inhibitors of the proteasome block the degradation of most cell proteins and the generation of peptides presented on MHC class I molecules.Cell. 1994;78:761–771.

    Article  PubMed  CAS  Google Scholar 

  245. Beraud C, Greene WC. Interaction of HTLV-I Tax with the human proteasome: implications for NF-kappa B induction.J Acquir Immune Defic Syndr Hum Retrovirol. 1996;13(suppl 1):S76-S84.

    Article  PubMed  CAS  Google Scholar 

  246. Petropoulos L, Hiscott J. Association between HTLV-1 Tax and I kappa B alpha is dependent on the I kappa B alpha phosphorylation state.Virology. 1998;252:189–199.

    Article  PubMed  CAS  Google Scholar 

  247. Rousset R, Desbois C, Bantignies F, Jalinot P. Effects on NF-kappa B1/p105 processing of the interaction between the HTLV-1 transactivator Tax and the proteasome.Nature. 1996;381:328–331.

    Article  PubMed  CAS  Google Scholar 

  248. Tan C, Waldmann TA. Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukemia.Cancer Res. 2002;62:1083–1086.

    PubMed  CAS  Google Scholar 

  249. Lomas M, Hanon E, Tanaka Y, Bangham CR, Gould KG. Presentation of a new H-2D(k)-restricted epitope in the Tax protein of human T-lymphotropic virus type I is enhanced by the proteasome inhibitor lactacystin.J Gen Virol. 2002;83:641–650.

    Article  PubMed  Google Scholar 

  250. Morgan DC, Ruscetti FW, Gallo RC. Selective in vitro growth of T lymphocytes from normal human bone marrows.Science. 1976;193:1007–1008.

    Article  PubMed  CAS  Google Scholar 

  251. Tsukasaki K, Krebs J, Nagai K, et al. Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course.Blood. 2001;97:3875–3881.

    Article  PubMed  CAS  Google Scholar 

  252. Migone TS, Lin JX, Cereseto A, et al. Constitutively activated JAKSTAT pathway in T-cells transformed with HTLV-I.Science. 1995;269:79–81.

    Article  PubMed  CAS  Google Scholar 

  253. Mulloy JC, Migone TS, Ross TM, et al. Human and simian T-cell leukemia viruses type 2 (HTLV-2 and STLV-2pan-p) transform T-cells independently of Jak/STAT activation.J Virol. 1998;72:4408–4412.

    PubMed  PubMed Central  CAS  Google Scholar 

  254. Xu XN, Screaton GR, Gotch FM, et al. Evasion of cytotoxic T lymphocyte (CTL) responses by nef-dependent induction of Fas ligand (CD95L) expression on simian immunodeficiency virus-infected cells.J Exp Med. 1997;186:7–16.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  255. Migone TS, Cacalano NA, Taylor N, Yi T, Waldmann TA, Johnston JA. Recruitment of SH2-containing protein tyrosine phosphatase SHP-1 to the interleukin 2 receptor: loss of SHP-1 expression in human T-lymphotropic virus type I-transformed T cells.Proc Natl Acad Sci U S A. 1998;95:3845–3850.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  256. Grassmann R, Dengler C, Muller-Fleckenstein I, et al. 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.Proc Natl Acad Sci U S A. 1989;86:3351–3355.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  257. Iwanaga Y, Tsukahara T, Ohashi T, et al. Human T-cell leukemia virus type 1 tax protein abrogates interleukin-2 dependence in a mouse T-cell line.J Virol. 1999;73:1271–1277.

    PubMed  PubMed Central  CAS  Google Scholar 

  258. Tanaka Y, Yoshida A, Tozawa H, Shida H, Nyunoya H, Shimotohno K. Production of a recombinant human T-cell leukemia virus type-I trans-activator (tax1) antigen and its utilization for generation of monoclonal antibodies against various epitopes on the tax1 antigen.Int J Cancer. 1991;48:623–630.

    Article  PubMed  CAS  Google Scholar 

  259. Kelly K, Davis P, Mitsuya H, et al. A high proportion of early response genes are constitutively activated in T cells by HTLV-I.Oncogene. 1992;7:1463–1470.

    PubMed  CAS  Google Scholar 

  260. Robek MD, Ratner L. Immortalization of CD4(+) and CD8(+) T lymphocytes by human T-cell leukemia virus type 1 Tax mutants expressed in a functional molecular clone.J Virol. 1999;73:4856–4865.

    PubMed  PubMed Central  CAS  Google Scholar 

  261. Rosin O, Koch C, Schmitt I, Semmes OJ, Jeang KT, Grassmann R. A human T-cell leukemia virus Tax variant incapable of activating NF-kappaB retains its immortalizing potential for primary T-lymphocytes.J Biol Chem. 1998;273:6698–6703.

    Article  PubMed  CAS  Google Scholar 

  262. Sallusto F, Lenig D, Forster R, Lipp M, Lanzavecchia A. Two subsets of memory T lymphocytes with distinct homing potentials and effector functions.Nature. 1999;401:708–712.

    Article  PubMed  CAS  Google Scholar 

  263. Nagai M, Brennan MB, Sakai JA, Mora CA, Jacobson S. CD8(+) T cells are an in vivo reservoir for human T-cell lymphotropic virus type I.Blood. 2001;98:1858–1861.

    Article  PubMed  CAS  Google Scholar 

  264. Richardson JH, Edwards AJ, Cruickshank JK, Rudge P, Dalgleish AG. In vivo cellular tropism of human T-cell leukemia virus type 1.J Virol. 1990;64:5682–5687.

    PubMed  PubMed Central  CAS  Google Scholar 

  265. Kazanji M, Ureta-Vidal A, Ozden S, et al. Lymphoid organs as a major reservoir for human T-cell leukemia virus type 1 in experimentally infected squirrel monkeys (Saimiri sciureus): provirus expression, persistence, and humoral and cellular immune responses.J Virol. 2000;74:4860–4867.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  266. Gessain A, Louie A, Gout O, Gallo RC, Franchini G. Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis/HTLV-I-associated myelopathy.J Virol. 1991;65:1628–1633.

    PubMed  PubMed Central  CAS  Google Scholar 

  267. Gabet AS, Mortreux F, Talarmin A, et al. High circulating proviral load with oligoclonal expansion of HTLV-1 bearing T cells in HTLV-1 carriers with strongyloidiasis.Oncogene. 2000;19:4954–4960.

    Article  PubMed  CAS  Google Scholar 

  268. Cavrois M, Leclercq I, Gout O, Gessain A, Wain-Hobson S, Wattel E. Persistent oligoclonal expansion of human T-cell leukemia virus type 1-infected circulating cells in patients with tropical spastic paraparesis/HTLV-1 associated myelopathy.Oncogene. 1998;17:77–82.

    Article  PubMed  CAS  Google Scholar 

  269. Hayashi J, Kishihara Y, Yoshimura E, et al. Correlation between human T cell lymphotropic virus type-1 andStrongyloides stercoralis infections and serum immunoglobulin E responses in residents of Okinawa, Japan.Am J Trop Med Hyg. 1997;56:71–75.

    Article  PubMed  CAS  Google Scholar 

  270. Clarke MF, Trainor CD, Mann DL, Gallo RC, Reitz MS. Methylation of human T-cell leukemia virus proviral DNA and viral RNA expression in short- and long-term cultures of infected cells.Virology. 1984;135:97–104.

    Article  PubMed  CAS  Google Scholar 

  271. Datta S, Kothari NH, Fan H. Induction of Tax i expression in MT-4 cells by 5-azacytidine leads to protein binding in the HTLV-1 LTR in vivo.Virology. 2001;283:207–214.

    Article  PubMed  CAS  Google Scholar 

  272. Koiwa T, Hamano-Usami A, Ishida T, et al. 5′-long terminal repeatselective CpG methylation of latent human T-cell leukemia virus type 1 provirus in vitro and in vivo.J Virol. 2002;76:9389–9397.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  273. Goon PK, Hanon E, Igakura T, et al. High frequencies of Th1-type CD4(+) T cells specific to HTLV-1 Env and Tax proteins in patients with HTLV-1-associated myelopathy/tropical spastic paraparesis.Blood. 2002;99:3335–3341.

    Article  PubMed  CAS  Google Scholar 

  274. Hanon E, Hall S, Taylor GP, et al. Abundant tax protein expression in CD4+ T cells infected with human T-cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes.Blood. 2000;95:1386–1392.

    PubMed  CAS  Google Scholar 

  275. Jacobson S, Raine CS, Mingioli ES, McFarlin DE. Isolation of an HTLV-1-like retrovirus from patients with tropical spastic paraparesis.Nature. 1988;331:540–543.

    Article  PubMed  CAS  Google Scholar 

  276. Nagai M, Kubota R, Greten TF, Schneck JP, Leist TP, Jacobson S. Increased activated human T cell lymphotropic virus type I (HTLV-I) Tax11-19-specific memory and effector CD8+ cells in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis: correlation with HTLV-I provirus load.J Infect Dis. 2001;183:197–205.

    Article  PubMed  CAS  Google Scholar 

  277. Asquith B, Hanon E, Taylor GP, Bangham CR. Is human T-cell lymphotropic virus type I really silent?Philos Trans R Soc Lond B Biol Sci. 2000;355:1013–1019.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  278. Hanon E, Stinchcombe JC, Saito M, et al. Fratricide among CD8(+) T lymphocytes naturally infected with human T cell lymphotropic virus type I.Immunity. 2000;13:657–664.

    Article  PubMed  CAS  Google Scholar 

  279. Hanon E, Asquith RE, Taylor GP, Tanaka Y, Weber JN, Bangham CR. High frequency of viral protein expression in human T cell lymphotropic virus type 1-infected peripheral blood mononuclear cells.AIDS Res Hum Retroviruses. 2000;16:1711–1715.

    Article  PubMed  CAS  Google Scholar 

  280. Kubota R, Furukawa Y, Izumo S, Usuku K, Osame M. Degenerate specificity of HTLV-I-specific CD8+ T cells during viral replication in patients with HTLV-I-associated myelopathy (HAM/TSP).Blood. 2003;101:3074–3081.

    Article  PubMed  CAS  Google Scholar 

  281. Lim DG, Bieganowska BK, Freeman GJ, Hafler DA. Examination of CD8+ T cell function in humans using MHC class I tetramers: similar cytotoxicity but variable proliferation and cytokine production among different clonal CD8+ T cells specific to a single viral epitope.J Immunol. 2000;165:6214–6220.

    Article  PubMed  CAS  Google Scholar 

  282. Feuerstein N, Firestein R, Aiyar N, He X, Murasko D, Cristofalo V. Late induction of CREB/ATF binding and a concomitant increase in cAMP levels in T and B lymphocytes stimulated via the antigen receptor.J Immunol. 1996;156:4582–4593.

    PubMed  CAS  Google Scholar 

  283. Ego T, Ariumi Y, Shimotohno K. The interaction of HTLV-1 Tax with HDAC1 negatively regulates the viral gene expression.Oncogene. 2002;21:7241–7246.

    Article  PubMed  CAS  Google Scholar 

  284. Sasada T, Nakamura H, Masutani H, et al. Thioredoxin-mediated redox control of human T cell lymphotropic virus type I (HTLV-I) gene expression.Mol Immunol. 2002;38:723–732.

    Article  PubMed  CAS  Google Scholar 

  285. Kamada N, Sakurai M, Miyamoto K, et al. Chromosome abnormalities in adult T-cell leukemia/lymphoma: a karyotype review committee report.Cancer Res. 1992;52:1481–1493.

    PubMed  CAS  Google Scholar 

  286. Mortreux F, Leclercq I, Gabet AS, et al. Somatic mutation in human T-cell leukemia virus type 1 provirus and flanking cellular sequences during clonal expansion in vivo.J Natl Cancer Inst. 2001;93:367–377.

    Article  PubMed  CAS  Google Scholar 

  287. Tsukasaki K. Genetic instability of adult T-cell leukemia/lymphoma by comparative genomic hybridization analysis.J Clin Immunol. 2002;22:57–63.

    Article  PubMed  CAS  Google Scholar 

  288. Niewiesk S, Daenke S, Parker CE, et al. The transactivator gene of human T-cell leukemia virus type I is more variable within and between healthy carriers than patients with tropical spastic paraparesis.J Virol. 1994;68:6778–6781.

    PubMed  PubMed Central  CAS  Google Scholar 

  289. Furukawa Y, Kubota R, Tara M, Izumo S, Osame M. Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia.Blood. 2001;97:987–993.

    Article  PubMed  CAS  Google Scholar 

  290. Morozov VA, Lagaye S, Taylor GP, Matutes E, Weiss RA. Chimeric matrix proteins encoded by defective proviruses with large internal deletions in human T-cell leukemia virus type 1-infected humans.J Virol. 2000;74:3933–3940.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  291. Ohshima K, Kikuchi M, Masuda Y, et al. Defective provirus form of human T-cell leukemia virus type I in adult T-cell leukemia/ lymphoma: clinicopathological features.Cancer Res. 1991;51:4639–4642.

    PubMed  CAS  Google Scholar 

  292. Okazaki S, Moriuchi R, Yosizuka N, et al. HTLV-1 proviruses encoding non-functional TAX in adult T-cell leukemia.Virus Genes. 2001;23:123–135.

    Article  PubMed  CAS  Google Scholar 

  293. Tamiya S, Matsuoka M, Etoh K, et al. Two types of defective human T-lymphotropic virus type I provirus in adult T-cell leukemia.Blood. 1996;88:3065–3073.

    PubMed  CAS  Google Scholar 

  294. Drexler HG. Review of alterations of the cyclin-dependent kinase inhibitors INK4 family genes p15, p16, p18 and p19 in human leukemia-lymphoma cells.Leukemia. 1998;12:845–859.

    Article  PubMed  CAS  Google Scholar 

  295. Fujiwara H, Arima N, Hashimoto-Tamaoki T, et al. Alteration of p16 (CDKN2) gene is associated with interleukin-2-induced tumor cell growth in adult T cell leukemia.Exp Hematol. 1999;27:1004–1009.

    Article  PubMed  CAS  Google Scholar 

  296. Hatta Y, Hirama T, Miller CW, Yamada Y, Tomonaga M, Koeffler HP. Homozygous deletions of p15 (MTS2) and p16 (CDKN2/MTS1) genes in adult T-cell leukemia.Blood. 1995;85:2699–2704.

    PubMed  CAS  Google Scholar 

  297. Hatta Y, Koeffler HP. Role of tumor suppressor genes in the development of adult T cell leukemia/lymphoma (ATLL).Leukemia. 2002;16:1069–1085.

    Article  PubMed  CAS  Google Scholar 

  298. Hoffman PM, Dhib-Jalbut S, Mikovits JA, et al. Human T-cell leukemia virus type I infection of monocytes and microglial cells in primary human cultures.Proc Natl Acad Sci U S A. 1992;89:11784–11788.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  299. Nosaka K, Maeda M, Tamiya S, Sakai T, Mitsuya H, Matsuoka M. Increasing methylation of the CDKN2A gene is associated with the progression of adult T-cell leukemia.Cancer Res. 2000;60:1043–1048.

    PubMed  CAS  Google Scholar 

  300. Pombo-de-Oliveira MS, Dobbin JA, Loureiro P, et al. Genetic mutation and early onset of T-cell leukemia in pediatric patients infected at birth with HTLV-I.Leuk Res. 2002;26:155–161.

    Article  PubMed  CAS  Google Scholar 

  301. Trovato R, Cereseto A, Takemoto S, et al. Deletion of the p16INK4A gene inex vivo acute ATLL cells and methylation of p16INK4A promoter in HTLV-I-infected T-cell lines.AIDS Res Hum Retroviruses. 2000;16:709–713.

    Article  PubMed  CAS  Google Scholar 

  302. Hatta Y, Yamada M, Tomonaga M, Koeffler HP. Extensive analysis of the retinoblastoma gene in adult T cell leukemia/lymphoma (ATL).Leukemia. 1997;11:984–989.

    Article  CAS  PubMed  Google Scholar 

  303. Sakashita A, Hattori T, Miller CW, et al. Mutations of the p53 gene in adult T-cell leukemia.Blood. 1992;79:477–480.

    PubMed  CAS  Google Scholar 

  304. Takemoto S, Trovato R, Cereseto A, et al. p53 stabilization and functional impairment in the absence of genetic mutation or the alteration of the p14(ARF)-MDM2 loop in ex vivo and cultured adult T-cell leukemia/lymphoma cells.Blood. 2000;95:3939–3944.

    PubMed  CAS  Google Scholar 

  305. Ohshima K, Haraoka S, Yoshioka S, et al. Mutation analysis of mitotic checkpoint genes (hBUB1 and hBUBR1) and microsatellite instability in adult T-cell leukemia/lymphoma.Cancer Lett. 2000;158:141–150.

    Article  PubMed  CAS  Google Scholar 

  306. Mori N, Yamada Y, Hata T, et al. Expression of survivin in HTLVI- infected T-cell lines and primary ATL cells.Biochem Biophys Res Commun. 2001;282:1110–1113.

    Article  PubMed  CAS  Google Scholar 

  307. Mori N, Inoue H, Yoshida T, Tanabe T, Yamamoto N. Constitutive expression of the cyclooxygenase-2 gene in T-cell lines infected with human T cell leukemia virus type I.Int J Cancer. 2001;94:813–819.

    Article  PubMed  CAS  Google Scholar 

  308. Takemoto S, Mulloy JC, Cereseto A, et al. Proliferation of adult T-cell leukemia/lymphoma cells is associated with the constitutive activation of JAK/STAT proteins.Proc Natl Acad Sci U S A. 1997;94:13897–13902.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Franchini, G., Fukumoto, R. & Fullen, J.R. T-Cell Control by Human T-Cell Leukemia/Lymphoma Virus Type 1. Int J Hematol 78, 280–296 (2003). https://doi.org/10.1007/BF02983552

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