1932
0
  1. Home
  2. A-Z Publications
  3. Annual Review of Immunology
  4. Volume 36, 2018
  5. Article

Annual Review of Immunology

Volume 36, 2018

Human T Cell Leukemia Virus Type 1: Persistence and Pathogenesis

Abstract

Human T cell leukemia virus type 1 (HTLV-1), also known as human T lymphotropic virus type 1, was the first exogenous human retrovirus discovered. Unlike the distantly related lentivirus HIV-1, HTLV-1 causes disease in only 5–10% of infected people, depending on their ethnic origin. But whereas HIV-1 infection and the consequent diseases can be efficiently contained in most cases by antiretroviral drug treatment, there is no satisfactory treatment for the malignant or inflammatory diseases caused by HTLV-1. The purpose of the present article is to review recent advances in the understanding of the mechanisms by which the virus persists in vivo and causes disabling or fatal diseases.

Keyword(s): ATL, HAM/TSP, HTLV-1, latency, retrovirus
Loading

Article metrics loading...

/content/journals/10.1146/annurev-immunol-042617-053222
2018-04-26
2024-04-20
Loading full text...

Full text loading...

/deliver/fulltext/immunol/36/1/annurev-immunol-042617-053222.html?itemId=/content/journals/10.1146/annurev-immunol-042617-053222&mimeType=html&fmt=ahah

Literature Cited

  1. Bangham CR, Araujo A, Yamano Y, Taylor GP. 1.  2015. HTLV-1-associated myelopathy/tropical spastic paraparesis. Nat. Rev. Dis. Primers 1:15012 [Google Scholar]
  2. Watanabe T. 2.  2017. Adult T-cell leukemia: molecular basis for clonal expansion and transformation of HTLV-1-infected T cells. Blood 129:1071–81 [Google Scholar]
  3. Coffin JM. 3.  2015. The discovery of HTLV-1, the first pathogenic human retrovirus. PNAS 112:15525–29 [Google Scholar]
  4. Gessain A, Cassar O. 4.  2012. Epidemiological aspects and world distribution of HTLV-1 infection. Front. Microbiol. 3:388 [Google Scholar]
  5. Matsuoka M, Jeang K-T. 5.  2011. Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax, HBZ, and therapy. Oncogene 30:1379–89 [Google Scholar]
  6. Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E. 6.  2007. Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect. Dis. 7:266–81 [Google Scholar]
  7. Yoshida M. 7.  2001. Multiple viral strategies of HTLV-1 for dysregulation of cell growth control. Annu. Rev. Immunol. 19:475–96 [Google Scholar]
  8. Fox JM, Mutalima N, Molyneux E, Carpenter LM, Taylor GP. 8.  et al. 2016. Seroprevalence of HTLV-1 and HTLV-2 amongst mothers and children in Malawi within the context of a systematic review and meta-analysis of HTLV seroprevalence in Africa. Trop. Med. Int. Health 21:312–24 [Google Scholar]
  9. Salehi M, Shokouhi Mostafavi SK, Ghasemian A, Gholami M, Kazemi-Vardanjani A, Rahimi MK. 9.  2017. Seroepidemiology of HTLV-1 and HTLV-2 infection in Neyshabur City, North-Eastern Iran, during 2010–2014. Iran Biomed. J. 21:57–60 [Google Scholar]
  10. Einsiedel L, Woodman RJ, Flynn M, Wilson K, Cassar O, Gessain A. 10.  2016. Human T-lymphotropic virus type 1 infection in an Indigenous Australian population: epidemiological insights from a hospital-based cohort study. BMC Public Health 16:787 [Google Scholar]
  11. Einsiedel LJ, Pham H, Woodman RJ, Pepperill C, Taylor KA. 11.  2016. The prevalence and clinical associations of HTLV-1 infection in a remote Indigenous community. Med. J. Aust. 205:305–9 [Google Scholar]
  12. Yanagihara R, Jenkins CL, Alexander SS, Mora CA, Garruto RM. 12.  1990. Human T lymphotropic virus type I infection in Papua New Guinea: high prevalence among the Hagahai confirmed by Western analysis. J. Infect. Dis. 162:649–54 [Google Scholar]
  13. Bangham CR. 13.  1993. Human T-cell leukaemia virus type I and neurological disease. Curr. Opin. Neurobiol. 3:773–78 [Google Scholar]
  14. Alvarez C, Gotuzzo E, Vandamme AM, Verdonck K. 14.  2016. Family aggregation of human T-lymphotropic virus 1-associated diseases: a systematic review. Front. Microbiol. 7:1674 [Google Scholar]
  15. Iwanaga M, Watanabe T, Utsunomiya A, Okayama A, Uchimaru K. 15.  et al. 2010. Human T-cell leukemia virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan. Blood 116:1211–19 [Google Scholar]
  16. Satake M, Iwanaga M, Sagara Y, Watanabe T, Okuma K, Hamaguchi I. 16.  2016. Incidence of human T-lymphotropic virus 1 infection in adolescent and adult blood donors in Japan: a nationwide retrospective cohort analysis. Lancet Infect. Dis. 16:1246–54 [Google Scholar]
  17. Satake M, Yamada Y, Atogami S, Yamaguchi K. 17.  2015. The incidence of adult T-cell leukemia/lymphoma among human T-lymphotropic virus type 1 carriers in Japan. Leuk. Lymphoma 56:1806–12 [Google Scholar]
  18. Yoshida N, Chihara D. 18.  2015. Incidence of adult T-cell leukemia/lymphoma in nonendemic areas. Curr. Treat. Options Oncol. 16:7 [Google Scholar]
  19. Bandeira LM, Uehara SN, Asato MA, Aguena GS, Maedo CM. 19.  et al. 2015. High prevalence of HTLV-1 infection among Japanese immigrants in non-endemic area of Brazil. PLOS Negl. Trop. Dis. 9:e0003691 [Google Scholar]
  20. 20. Eur. Cent. Dis. Prev. Control (ECDC). 2015. Geographical Distribution of Areas with a High Prevalence of HTLV-1 Infection Stockholm: ECDC https://doi.org/10.2900/047633 [Crossref]
  21. Cook LB, Melamed A, Demontis MA, Laydon DJ, Fox JM. 21.  et al. 2016. Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients. Retrovirology 13:3 [Google Scholar]
  22. Murphy EL. 22.  2016. Infection with human T-lymphotropic virus types-1 and -2 (HTLV-1 and -2): implications for blood transfusion safety. Transfus. Clin. Biol. 23:13–19 [Google Scholar]
  23. Willems L, Hasegawa H, Accolla R, Bangham C, Bazarbachi A. 23.  et al. 2017. Reducing the global burden of HTLV-1 infection: an agenda for research and action. Antiviral Res 137:41–48 [Google Scholar]
  24. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H. 24.  1977. Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood 50:481–92 [Google Scholar]
  25. Ishitsuka K, Tamura K. 25.  2014. Human T-cell leukaemia virus type I and adult T-cell leukaemia-lymphoma. Lancet Oncol 15:e517–26 [Google Scholar]
  26. Shimoyama M. 26.  1991. Diagnostic criteria and classification of clinical subtypes of adult T-cell leukaemia-lymphoma: a report from the Lymphoma Study Group (1984–87). Br. J. Haematol. 79:428–37 [Google Scholar]
  27. Katsuya H, Ishitsuka K, Utsunomiya A, Hanada S, Eto T. 27.  et al.; for ATL-Progn. Index Proj. 2015. Treatment and survival among 1594 patients with ATL. Blood 126:2570–77 [Google Scholar]
  28. Tsukasaki K, Tobinai K. 28.  2014. Human T-cell lymphotropic virus type I-associated adult T-cell leukemia-lymphoma: new directions in clinical research. Clin. Cancer Res. 20:5217–25 [Google Scholar]
  29. Utsunomiya A, Choi I, Chihara D, Seto M. 29.  2015. Recent advances in the treatment of adult T-cell leukemia-lymphomas. Cancer Sci 106:344–51 [Google Scholar]
  30. Bazarbachi A, Plumelle Y, Carlos Ramos J, Tortevoye P, Otrock Z. 30.  et al. 2010. Meta-analysis on the use of zidovudine and interferon-alfa in adult T-cell leukemia/lymphoma showing improved survival in the leukemic subtypes. J. Clin. Oncol. 28:4177–83 [Google Scholar]
  31. Phillips EH, Hodson A, Hermine O, Bazarbachi A, Cwynarski K. 31.  2016. Striving to cure adult T-cell leukaemia/lymphoma: a role for allogeneic stem cell transplant?. Bone Marrow Transpl 51:1549–55 [Google Scholar]
  32. Iwasaki Y. 32.  1993. Human T cell leukemia virus type I infection and chronic myelopathy. Brain Pathol 3:1–10 [Google Scholar]
  33. Iwasaki Y, Ohara Y, Kobayashi I, Akizuki S. 33.  1992. Infiltration of helper/inducer T lymphocytes heralds central nervous system damage in human T-cell leukemia virus infection. Am. J. Pathol. 140:1003–8 [Google Scholar]
  34. Matsuura E, Kubota R, Tanaka Y, Takashima H, Izumo S. 34.  2015. Visualization of HTLV-1-specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis. J. Neuropathol. Exp. Neurol. 74:2–14 [Google Scholar]
  35. Ohshima K. 35.  2007. Pathological features of diseases associated with human T-cell leukemia virus type I. Cancer Sci 98:772–6 [Google Scholar]
  36. Mochizuki M, Watanabe T, Yamaguchi K, Tajima K, Yoshimura K. 36.  et al. 1992. Uveitis associated with human T lymphotropic virus type I: seroepidemiologic, clinical, and virologic studies. J. Infect. Dis. 166:943–44 [Google Scholar]
  37. Morgan OS, Rodgers-Johnson P, Mora C, Char G. 37.  1989. HTLV-1 and polymyositis in Jamaica. Lancet 2:1184–87 [Google Scholar]
  38. Lee R, Schwartz RA. 38.  2011. Human T-lymphotrophic virus type 1-associated infective dermatitis: a comprehensive review. J. Am. Acad. Dermatol. 64:152–60 [Google Scholar]
  39. Nishioka K. 39.  1996. HTLV-I arthropathy and Sjogren syndrome. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 13:Suppl. 1S57–62 [Google Scholar]
  40. Nishioka K, Maruyama I, Sato K, Kitajima I, Nakajima Y, Osame M. 40.  1989. Chronic inflammatory arthropathy associated with HTLV-I. Lancet 1:441 [Google Scholar]
  41. Einsiedel L, Fernandes L, Spelman T, Steinfort D, Gotuzzo E. 41.  2012. Bronchiectasis is associated with human T-lymphotropic virus 1 infection in an Indigenous Australian population. Clin. Infect. Dis. 54:43–50 [Google Scholar]
  42. Einsiedel L, Spelman T, Goeman E, Cassar O, Arundell M, Gessain A. 42.  2014. Clinical associations of human T-lymphotropic virus type 1 infection in an Indigenous Australian population. PLOS Negl. Trop. Dis. 8:e2643 [Google Scholar]
  43. Honarbakhsh S, Taylor GP. 43.  2015. High prevalence of bronchiectasis is linked to HTLV-1-associated inflammatory disease. BMC Infect. Dis. 15:258 [Google Scholar]
  44. Okada F, Ando Y, Yoshitake S, Yotsumoto S, Matsumoto S. 44.  et al. 2006. Pulmonary CT findings in 320 carriers of human T-lymphotropic virus type 1. Radiology 240:559–64 [Google Scholar]
  45. Yamashiro T, Kamiya H, Miyara T, Gibo S, Ogawa K. 45.  et al. 2012. CT scans of the chest in carriers of human T-cell lymphotropic virus type 1: presence of interstitial pneumonia. Acad. Radiol. 19:952–57 [Google Scholar]
  46. Verdonck K, Gonzalez E, Henostroza G, Nabeta P, Llanos F. 46.  et al. 2007. HTLV-1 infection is frequent among out-patients with pulmonary tuberculosis in northern Lima, Peru. Int. J. Tuberc. Lung Dis. 11:1066–72 [Google Scholar]
  47. Gotuzzo E, Terashima A, Alvarez H, Tello R, Infante R. 47.  et al. 1999. Strongyloides stercoralis hyperinfection associated with human T cell lymphotropic virus type-1 infection in Peru. Am. J. Trop. Med. Hyg. 60:146–49 [Google Scholar]
  48. LaGrenade L, Hanchard B, Fletcher V, Cranston B, Blattner W. 48.  1990. Infective dermatitis of Jamaican children: a marker for HTLV-I infection. Lancet 336:1345–57 [Google Scholar]
  49. Bittencourt AL, Oliveira MFP. 49.  2010. Cutaneous manifestations associated with HTLV-1 infection. Int. J. Dermatol. 49:1099–110 [Google Scholar]
  50. Einsiedel L, Cassar O, Spelman T, Joseph S, Gessain A. 50.  2016. Higher HTLV-1c proviral loads are associated with blood stream infections in an Indigenous Australian population. J. Clin. Virol. 78:93–98 [Google Scholar]
  51. Bangham CR. 51.  2009. CTL quality and the control of human retroviral infections. Eur. J. Immunol. 39:1700–12 [Google Scholar]
  52. Barnard AL, Igakura T, Tanaka Y, Taylor GP, Bangham CR. 52.  2005. Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1-infected lymphocytes. Blood 106:988–95 [Google Scholar]
  53. Nejmeddine M, Negi VS, Mukherjee S, Tanaka Y, Orth K. 53.  et al. 2009. HTLV-1-Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse. Blood 114:1016–25 [Google Scholar]
  54. Igakura T, Stinchcombe JC, Goon PK, Taylor GP, Weber JN. 54.  et al. 2003. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. Science 299:1713–16 [Google Scholar]
  55. Majorovits E, Nejmeddine M, Tanaka Y, Taylor GP, Fuller SD, Bangham CR. 55.  2008. Human T-lymphotropic virus-1 visualized at the virological synapse by electron tomography. PLOS ONE 3:e2251 [Google Scholar]
  56. Pais-Correia AM, Sachse M, Guadagnini S, Robbiati V, Lasserre R. 56.  et al. 2010. Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses. Nat. Med. 16:83–89 [Google Scholar]
  57. Gross C, Wiesmann V, Millen S, Kalmer M, Wittenberg T. 57.  et al. 2016. The Tax-inducible actin-bundling protein fascin is crucial for release and cell-to-cell transmission of human T-cell leukemia virus type 1 (HTLV-1). PLOS Pathog 12:e1005916 [Google Scholar]
  58. Cao S, Maldonado JO, Grigsby IF, Mansky LM, Zhang W. 58.  2015. Analysis of human T-cell leukemia virus type 1 particles by using cryo-electron tomography. J. Virol. 89:2430–35 [Google Scholar]
  59. Martin JL, Cao S, Maldonado JO, Zhang W, Mansky LM. 59.  2016. Distinct particle morphologies revealed through comparative parallel analyses of retrovirus-like particles. J. Virol. 90:8074–84 [Google Scholar]
  60. Miyoshi I, Kubonishi I, Yoshimoto S, Akagi T, Ohtsuki Y. 60.  et al. 1981. Type C virus particles in a cord T-cell line derived by co-cultivating normal human cord leukocytes and human leukaemic T cells. Nature 294:770–71 [Google Scholar]
  61. Delamarre L, Pique C, Rosenberg AR, Blot V, Grange MP. 61.  et al. 1999. The Y-S-L-I tyrosine-based motif in the cytoplasmic domain of the human T-cell leukemia virus type 1 envelope is essential for cell-to-cell transmission. J. Virol. 73:9659–63 [Google Scholar]
  62. Derse D, Hill SA, Lloyd PA, Chung H, Morse BA. 62.  2001. Examining human T-lymphotropic virus type 1 infection and replication by cell-free infection with recombinant virus vectors. J. Virol. 75:8461–68 [Google Scholar]
  63. Dutartre H, Claviere M, Journo C, Mahieux R. 63.  2016. Cell-free versus cell-to-cell infection by human immunodeficiency virus type 1 and human T-lymphotropic virus type 1: exploring the link among viral source, viral trafficking, and viral replication. J. Virol. 90:7607–17 [Google Scholar]
  64. Jones KS, Petrow-Sadowski C, Huang YK, Bertolette DC, Ruscetti FW. 64.  2008. Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4+ T cells. Nat. Med. 14:429–36 [Google Scholar]
  65. Alais S, Mahieux R, Dutartre H. 65.  2015. Viral source-independent high susceptibility of dendritic cells to human T-cell leukemia virus type 1 infection compared to that of T lymphocytes. J. Virol. 89:10580–90 [Google Scholar]
  66. Van Prooyen N, Gold H, Andresen V, Schwartz O, Jones K. 66.  et al. 2010. Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission. PNAS 107:20738–43 [Google Scholar]
  67. Filippone C, Betsem E, Tortevoye P, Cassar O, Bassot S. 67.  et al. 2015. A severe bite from a nonhuman primate is a major risk factor for HTLV-1 infection in hunters from Central Africa. Clin. Infect. Dis. 60:1667–76 [Google Scholar]
  68. Overbaugh J, Bangham CR. 68.  2001. Selection forces and constraints on retroviral sequence variation. Science 292:1106–9 [Google Scholar]
  69. Wattel E, Cavrois M, Gessain A, Wain-Hobson S. 69.  1996. Clonal expansion of infected cells: a way of life for HTLV-I. J. Acquir. Immune Defic. Syndr. Hum. Retrovirol. 13:Suppl. 1S92–9 [Google Scholar]
  70. Gillet NA, Malani N, Melamed A, Gormley N, Carter R. 70.  et al. 2011. The host genomic environment of the provirus determines the abundance of HTLV-1-infected T cell clones. Blood 117:3113–22 [Google Scholar]
  71. Laydon DJ, Melamed A, Sim A, Gillet NA, Sim K. 71.  et al. 2014. Quantification of HTLV-1 clonality and TCR diversity. PLOS Comput. Biol. 10:e1003646 [Google Scholar]
  72. Furukawa Y, Fujisawa J, Osame M, Toita M, Sonoda S. 72.  et al. 1992. Frequent clonal proliferation of human T-cell leukemia virus type 1 (HTLV-1)-infected T cells in HTLV-1-associated myelopathy (HAM-TSP). Blood 80:1012–16 [Google Scholar]
  73. Takemoto S, Matsuoka M, Yamaguchi K, Takatsuki K. 73.  1994. A novel diagnostic method of adult T-cell leukemia: monoclonal integration of human T-cell lymphotropic virus type I provirus DNA detected by inverse polymerase chain reaction. Blood 84:3080–85 [Google Scholar]
  74. Bangham CR, Cook LB, Melamed A. 74.  2014. HTLV-1 clonality in adult T-cell leukaemia and non-malignant HTLV-1 infection. Semin. Cancer Biol. 26C:89–98 [Google Scholar]
  75. Firouzi S, Lopez Y, Suzuki Y, Nakai K, Sugano S. 75.  et al. 2014. Development and validation of a new high-throughput method to investigate the clonality of HTLV-1-infected cells based on provirus integration sites. Genome Med 6:46 [Google Scholar]
  76. Cook LB, Rowan AG, Melamed A, Taylor GP, Bangham CR. 76.  2012. HTLV-1-infected T cells contain a single integrated provirus in natural infection. Blood 120:3488–90 [Google Scholar]
  77. Kirk PD, Huvet M, Melamed A, Maertens GN, Bangham CR. 77.  2016. Retroviruses integrate into a shared, non-palindromic DNA motif. Nat. Microbiol. 2:16212 [Google Scholar]
  78. Melamed A, Laydon DJ, Gillet NA, Tanaka Y, Taylor GP, Bangham CR. 78.  2013. Genome-wide determinants of proviral targeting, clonal abundance and expression in natural HTLV-1 infection. PLOS Pathog 9:e1003271 [Google Scholar]
  79. Maertens GN. 79.  2016. B′-protein phosphatase 2A is a functional binding partner of delta-retroviral integrase. Nucleic Acids Res 44:364–76 [Google Scholar]
  80. Melamed A, Laydon DJ, Al Khatib H, Rowan AG, Taylor GP, Bangham CR. 80.  2015. HTLV-1 drives vigorous clonal expansion of infected CD8+ T cells in natural infection. Retrovirology 12:91 [Google Scholar]
  81. Melamed A, Witkover AD, Laydon DJ, Brown R, Ladell K. 81.  et al. 2014. Clonality of HTLV-2 in natural infection. PLOS Pathog 10:e1004006 [Google Scholar]
  82. Taniguchi Y, Nosaka K, Yasunaga J, Maeda M, Mueller N. 82.  et al. 2005. Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms. Retrovirology 2:64 [Google Scholar]
  83. Cook LB, Melamed A, Niederer H, Valganon M, Laydon D. 83.  et al. 2014. The role of HTLV-1 clonality, proviral structure, and genomic integration site in adult T-cell leukemia/lymphoma. Blood 123:3925–31 [Google Scholar]
  84. Padeken J, Heun P. 84.  2014. Nucleolus and nuclear periphery: Velcro for heterochromatin. Curr. Opin. Cell Biol. 28:54–60 [Google Scholar]
  85. Pique C, Ureta-Vidal A, Gessain A, Chancerel B, Gout O. 85.  et al. 2000. Evidence for the chronic in vivo production of human T cell leukemia virus type I Rof and Tof proteins from cytotoxic T lymphocytes directed against viral peptides. J. Exp. Med. 191:567–72 [Google Scholar]
  86. Bai XT, Nicot C. 86.  2012. Overview on HTLV-1 p12, p8, p30, p13: accomplices in persistent infection and viral pathogenesis. Front. Microbiol. 3:400 [Google Scholar]
  87. Pise-Masison CA, Castro-Amarante MF, Enose-Akahata Y, Buchmann RC, Fenizia C. 87.  et al. 2014. Co-dependence of HTLV-1 p12 and p8 functions in virus persistence. PLOS Pathog 10:e1004454 [Google Scholar]
  88. Silic-Benussi M, Biasiotto R, Andresen V, Franchini G, D'Agostino DM, Ciminale V. 88.  2010. HTLV-1 p13, a small protein with a busy agenda. Mol. Aspects Med. 31:350–58 [Google Scholar]
  89. Valeri VW, Hryniewicz A, Andresen V, Jones K, Fenizia C. 89.  et al. 2010. Requirement of the human T-cell leukemia virus p12 and p30 products for infectivity of human dendritic cells and macaques but not rabbits. Blood 116:3809–17 [Google Scholar]
  90. Derse D, Mikovits J, Ruscetti F. 90.  1997. 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 237:123–28 [Google Scholar]
  91. Furukawa Y, Usuku K, Izumo S, Osame M. 91.  2004. Human T cell lymphotropic virus type I (HTLV-I) p12I is dispensable for HTLV-I transmission and maintenance of infection in vivo. AIDS Res. Hum. Retrovir. 20:1092–99 [Google Scholar]
  92. Van Dooren S, Meertens L, Lemey P, Gessain A, Vandamme AM. 92.  2005. Full-genome analysis of a highly divergent simian T-cell lymphotropic virus type 1 strain in Macaca arctoides. J. Gen. Virol. 86:1953–59 [Google Scholar]
  93. Giam CZ, Semmes OJ. 93.  2016. HTLV-1 infection and adult T-cell leukemia/lymphoma—a tale of two proteins: Tax and HBZ. Viruses 8:161 [Google Scholar]
  94. Grassmann R, Aboud M, Jeang KT. 94.  2005. Molecular mechanisms of cellular transformation by HTLV-1 Tax. Oncogene 24:5976–85 [Google Scholar]
  95. Matsuoka M, Jeang KT. 95.  2007. Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat. Rev. Cancer 7:270–80 [Google Scholar]
  96. Matsuoka M, Jeang KT. 96.  2011. Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: viral infectivity, Tax, HBZ and therapy. Oncogene 30:1379–89 [Google Scholar]
  97. Kataoka K, Nagata Y, Kitanaka A, Shiraishi Y, Shimamura T. 97.  et al. 2015. Integrated molecular analysis of adult T cell leukemia/lymphoma. Nat. Genet. 47:1304–15 [Google Scholar]
  98. Lemoine FJ, Marriott SJ. 98.  2002. Genomic instability driven by the human T-cell leukemia virus type I (HTLV-I) oncoprotein, Tax. Oncogene 21:7230–34 [Google Scholar]
  99. Tsukasaki K, Krebs J, Nagai K, Tomonaga M, Koeffler HP. 99.  et al. 2001. Comparative genomic hybridization analysis in adult T-cell leukemia/lymphoma: correlation with clinical course. Blood 97:3875–81 [Google Scholar]
  100. Baydoun HH, Cherian MA, Green P, Ratner L. 100.  2015. Inducible nitric oxide synthase mediates DNA double strand breaks in human T-cell leukemia virus type 1-induced leukemia/lymphoma. Retrovirology 12:71 [Google Scholar]
  101. Ho YK, Zhi H, Bowlin T, Dorjbal B, Philip S. 101.  et al. 2015. HTLV-1 Tax stimulates ubiquitin E3 ligase, ring finger protein 8, to assemble lysine 63-linked polyubiquitin chains for TAK1 and IKK activation. PLOS Pathog 11:e1005102 [Google Scholar]
  102. Pujari R, Hunte R, Thomas R, van der Weyden L, Rauch D. 102.  et al. 2015. Human T-cell leukemia virus type 1 (HTLV-1) Tax requires CADM1/TSLC1 for inactivation of the NF-κB inhibitor A20 and constitutive NF-κB signaling. PLOS Pathog 11:e1004721 [Google Scholar]
  103. Shibata Y, Tokunaga F, Goto E, Komatsu G, Gohda J. 103.  et al. 2017. HTLV-1 Tax induces formation of the active macromolecular IKK complex by generating Lys63- and Met1-linked hybrid polyubiquitin chains. PLOS Pathog 13:e1006162 [Google Scholar]
  104. Wang C, Long W, Peng C, Hu L, Zhang Q. 104.  et al. 2016. HTLV-1 Tax functions as a ubiquitin E3 ligase for direct IKK activation via synthesis of mixed-linkage polyubiquitin chains. PLOS Pathog 12:e1005584 [Google Scholar]
  105. Manivannan K, Rowan AG, Tanaka Y, Taylor GP, Bangham CR. 105.  2016. CADM1/TSLC1 identifies HTLV-1-infected cells and determines their susceptibility to CTL-mediated lysis. PLOS Pathog 12:e1005560 [Google Scholar]
  106. Cherian MA, Baydoun HH, Al-Saleem J, Shkriabai N, Kvaratskhelia M. 106.  et al. 2015. Akt pathway activation by human T-cell leukemia virus type 1 Tax oncoprotein. J. Biol. Chem. 290:26270–81 [Google Scholar]
  107. Takachi T, Takahashi M, Takahashi-Yoshita M, Higuchi M, Obata M. 107.  et al. 2015. Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells. Cancer Sci 106:461–65 [Google Scholar]
  108. Boxus M, Willems L. 108.  2012. How the DNA damage response determines the fate of HTLV-1 Tax-expressing cells. Retrovirology 9:2 [Google Scholar]
  109. Kinjo T, Ham-Terhune J, Peloponese JM Jr., Jeang KT. 109.  2010. Induction of reactive oxygen species by human T-cell leukemia virus type 1 Tax correlates with DNA damage and expression of cellular senescence marker. J. Virol. 84:5431–37 [Google Scholar]
  110. Liang MH, Geisbert T, Yao Y, Hinrichs SH, Giam CZ. 110.  2002. Human T-lymphotropic virus type 1 oncoprotein Tax promotes S-phase entry but blocks mitosis. J. Virol. 76:4022–33 [Google Scholar]
  111. Zhi H, Yang L, Kuo YL, Ho YK, Shih HM, Giam CZ. 111.  2011. NF-κB hyperactivation by HTLV-1 Tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ. PLOS Pathog 7:e1002025 [Google Scholar]
  112. Gorgoulis VG, Halazonetis TD. 112.  2010. Oncogene-induced senescence: the bright and dark side of the response. Curr. Opin. Cell Biol. 22:816–27 [Google Scholar]
  113. Laverdure S, Polakowski N, Hoang K, Lemasson I. 113.  2016. Permissive sense and antisense transcription from the 5′ and 3′ long terminal repeats of human T-cell leukemia virus type 1. J. Virol. 90:3600–10 [Google Scholar]
  114. Larocca D, Chao LA, Seto MH, Brunck TK. 114.  1989. Human T-cell leukemia virus minus strand transcription in infected T-cells. Biochem. Biophys. Res. Commun. 163:1006–13 [Google Scholar]
  115. Gaudray G, Gachon F, Basbous J, Biard-Piechaczyk M, Devaux C, Mesnard JM. 115.  2002. 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. 76:12813–22 [Google Scholar]
  116. Ma G, Yasunaga J, Matsuoka M. 116.  2016. Multifaceted functions and roles of HBZ in HTLV-1 pathogenesis. Retrovirology 13:16 [Google Scholar]
  117. Matsuoka M, Green PL. 117.  2009. The HBZ gene, a key player in HTLV-1 pathogenesis. Retrovirology 6:71 [Google Scholar]
  118. Yoshida M, Satou Y, Yasunaga J, Fujisawa J, Matsuoka M. 118.  2008. Transcriptional control of spliced and unspliced human T-cell leukemia virus type 1 bZIP factor (HBZ) gene. J. Virol. 82:9359–68 [Google Scholar]
  119. Furukawa Y, Kubota R, Tara M, Izumo S, Osame M. 119.  2001. Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia. Blood 97:987–93 [Google Scholar]
  120. Koiwa T, Hamano-Usami A, Ishida T, Okayama A, Yamaguchi K. 120.  et al. 2002. 5′-long terminal repeat-selective CpG methylation of latent human T-cell leukemia virus type 1 provirus in vitro and in vivo. J. Virol. 76:9389–97 [Google Scholar]
  121. Takeda S, Maeda M, Morikawa S, Taniguchi Y, Yasunaga J. 121.  et al. 2004. Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells. Int. J. Cancer 109:559–67 [Google Scholar]
  122. Miyazaki M, Yasunaga J, Taniguchi Y, Tamiya S, Nakahata T, Matsuoka M. 122.  2007. Preferential selection of human T-Cell leukemia virus type 1 provirus lacking the 5′ long terminal repeat during oncogenesis. J. Virol. 81:5714–23 [Google Scholar]
  123. Tamiya S, Matsuoka M, Etoh K, Watanabe T, Kamihira S. 123.  et al. 1996. Two types of defective human T-lymphotropic virus type I provirus in adult T-cell leukemia. Blood 88:3065–73 [Google Scholar]
  124. Satou Y, Yasunaga J, Yoshida M, Matsuoka M. 124.  2006. HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells. PNAS 103:720–25 [Google Scholar]
  125. MacNamara A, Rowan A, Hilburn S, Kadolsky U, Fujiwara H. 125.  et al. 2010. HLA class I binding of HBZ determines outcome in HTLV-1 infection. PLOS Pathog 6:e1001117 [Google Scholar]
  126. Hilburn S, Rowan A, Demontis MA, MacNamara A, Asquith B. 126.  et al. 2011. In vivo expression of human T-lymphotropic virus type 1 basic leucine-zipper protein generates specific CD8+ and CD4+ T-lymphocyte responses that correlate with clinical outcome. J. Infect. Dis. 203:529–36 [Google Scholar]
  127. Sugata K, Yasunaga J, Mitobe Y, Miura M, Miyazato P. 127.  et al. 2015. Protective effect of cytotoxic T lymphocytes targeting HTLV-1 bZIP factor. Blood 126:1095–105 [Google Scholar]
  128. Arnold J, Yamamoto B, Li M, Phipps AJ, Younis I. 128.  et al. 2006. Enhancement of infectivity and persistence in vivo by HBZ, a natural antisense coded protein of HTLV-1. Blood 107:3976–82 [Google Scholar]
  129. Lemasson I, Lewis MR, Polakowski N, Hivin P, Cavanagh MH. 129.  et al. 2007. Human T-cell leukemia virus type 1 (HTLV-1) bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription. J. Virol. 81:1543–53 [Google Scholar]
  130. Mitobe Y, Yasunaga J, Furuta R, Matsuoka M. 130.  2015. HTLV-1 bZIP factor RNA and protein impart distinct functions on T-cell proliferation and survival. Cancer Res 75:4143–52 [Google Scholar]
  131. Murphy J, Hall WW, Ratner L, Sheehy N. 131.  2016. Novel interactions between the HTLV antisense proteins HBZ and APH-2 and the NFAR protein family: implications for the HTLV lifecycles. Virology 494:129–42 [Google Scholar]
  132. Che XF, Zheng CL, Owatari S, Mutoh M, Gotanda T. 132.  et al. 2006. Overexpression of survivin in primary ATL cells and sodium arsenite induces apoptosis by down-regulating survivin expression in ATL cell lines. Blood 107:4880–87 [Google Scholar]
  133. Kamihira S, Yamada Y, Hirakata Y, Tomonaga M, Sugahara K. 133.  et al. 2001. Aberrant expression of caspase cascade regulatory genes in adult T-cell leukaemia: survivin is an important determinant for prognosis. Br. J. Haematol. 114:63–69 [Google Scholar]
  134. Kuhlmann AS, Villaudy J, Gazzolo L, Castellazzi M, Mesnard JM, Duc Dodon M. 134.  2007. HTLV-1 HBZ cooperates with JunD to enhance transcription of the human telomerase reverse transcriptase gene (hTERT). Retrovirology 4:92 [Google Scholar]
  135. Kinosada H, Yasunaga JI, Shimura K, Miyazato P, Onishi C. 135.  et al. 2017. HTLV-1 bZIP factor enhances T-cell proliferation by impeding the suppressive signaling of co-inhibitory receptors. PLOS Pathog 13:e1006120 [Google Scholar]
  136. Bangham CR, Ratner L. 136.  2015. How does HTLV-1 cause adult T-cell leukaemia/lymphoma (ATL)?. Curr. Opin. Virol. 14:93–100 [Google Scholar]
  137. Matsuoka M, Yasunaga J. 137.  2013. Human T-cell leukemia virus type 1: replication, proliferation and propagation by Tax and HTLV-1 bZIP factor. Curr. Opin. Virol. 3:684–91 [Google Scholar]
  138. Zhao T, Yasunaga J, Satou Y, Nakao M, Takahashi M. 138.  et al. 2009. Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-κB. Blood 113:2755–64 [Google Scholar]
  139. Hagiya K, Yasunaga J, Satou Y, Ohshima K, Matsuoka M. 139.  2011. ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells. Retrovirology 8:19 [Google Scholar]
  140. Ma G, Yasunaga J, Fan J, Yanagawa S, Matsuoka M. 140.  2013. HTLV-1 bZIP factor dysregulates the Wnt pathways to support proliferation and migration of adult T-cell leukemia cells. Oncogene 32:4222–30 [Google Scholar]
  141. Sugata K, Yasunaga J, Kinosada H, Mitobe Y, Furuta R. 141.  et al. 2016. HTLV-1 viral factor HBZ induces CCR4 to promote T-cell migration and proliferation. Cancer Res 76:5068–79 [Google Scholar]
  142. Toulza F, Nosaka K, Tanaka Y, Schioppa T, Balkwill F. 142.  et al. 2010. Human T-lymphotropic virus type 1-induced CC chemokine ligand 22 maintains a high frequency of functional FoxP3+ regulatory T cells. J. Immunol. 185:183–89 [Google Scholar]
  143. Vernin C, Thenoz M, Pinatel C, Gessain A, Gout O. 143.  et al. 2014. HTLV-1 bZIP factor HBZ promotes cell proliferation and genetic instability by activating OncomiRs. Cancer Res 74:6082–93 [Google Scholar]
  144. Yamamoto-Taguchi N, Satou Y, Miyazato P, Ohshima K, Nakagawa M. 144.  et al. 2013. HTLV-1 bZIP factor induces inflammation through labile Foxp3 expression. PLOS Pathog 9:e1003630 [Google Scholar]
  145. Satou Y, Yasunaga J, Zhao T, Yoshida M, Miyazato P. 145.  et al. 2011. HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo. PLOS Pathog 7:e1001274 [Google Scholar]
  146. Kawatsuki A, Yasunaga JI, Mitobe Y, Green PL, Matsuoka M. 146.  2016. HTLV-1 bZIP factor protein targets the Rb/E2F-1 pathway to promote proliferation and apoptosis of primary CD4+ T cells. Oncogene 35:4509–17 [Google Scholar]
  147. Wright DG, Marchal C, Hoang K, Ankney JA, Nguyen ST. 147.  et al. 2016. Human T-cell leukemia virus type-1-encoded protein HBZ represses p53 function by inhibiting the acetyltransferase activity of p300/CBP and HBO1. Oncotarget 7:1687–706 [Google Scholar]
  148. Bangham CR, Osame M. 148.  2005. Cellular immune response to HTLV-1. Oncogene 24:6035–46 [Google Scholar]
  149. Journo C, Mahieux R. 149.  2011. HTLV-1 and innate immunity. Viruses 3:1374–94 [Google Scholar]
  150. Charoenthongtrakul S, Zhou Q, Shembade N, Harhaj NS, Harhaj EW. 150.  2011. Human T cell leukemia virus type 1 tax inhibits innate antiviral signaling via NF-κB-dependent induction of SOCS1. J. Virol. 85:6955–62 [Google Scholar]
  151. Oliere S, Hernandez E, Lezin A, Arguello M, Douville R. 151.  et al. 2010. HTLV-1 evades type I interferon antiviral signaling by inducing the suppressor of cytokine signaling 1 (SOCS1). PLOS Pathog 6:e1001177 [Google Scholar]
  152. Fan J, Ma G, Nosaka K, Tanabe J, Satou Y. 152.  et al. 2010. APOBEC3G generates nonsense mutations in human T-cell leukemia virus type 1 proviral genomes in vivo. J. Virol. 84:7278–87 [Google Scholar]
  153. Derse D, Hill SA, Princler G, Lloyd P, Heidecker G. 153.  2007. Resistance of human T cell leukemia virus type 1 to APOBEC3G restriction is mediated by elements in nucleocapsid. PNAS 104:2915–20 [Google Scholar]
  154. Pollack RA, Jones RB, Pertea M, Bruner KM, Martin AR. 154.  et al. 2017. Defective HIV-1 proviruses are expressed and can be recognized by cytotoxic T lymphocytes, which shape the proviral landscape. Cell Host Microbe 21:494–506.e4 [Google Scholar]
  155. Neil SJ. 155.  2013. The antiviral activities of tetherin. Curr. Top. Microbiol. Immunol. 371:67–104 [Google Scholar]
  156. Ilinskaya A, Derse D, Hill S, Princler G, Heidecker G. 156.  2013. Cell-cell transmission allows human T-lymphotropic virus 1 to circumvent tetherin restriction. Virology 436:201–9 [Google Scholar]
  157. Goldstone DC, Ennis-Adeniran V, Hedden JJ, Groom HC, Rice GI. 157.  et al. 2011. HIV-1 restriction factor SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase. Nature 480:379–82 [Google Scholar]
  158. Sze A, Belgnaoui SM, Olagnier D, Lin R, Hiscott J, van Grevenynghe J. 158.  2013. Host restriction factor SAMHD1 limits human T cell leukemia virus type 1 infection of monocytes via STING-mediated apoptosis. Cell Host Microbe 14:422–34 [Google Scholar]
  159. Koyanagi Y, Itoyama Y, Nakamura N, Takamatsu K, Kira J. 159.  et al. 1993. In vivo infection of human T-cell leukemia virus type I in non-T cells. Virology 196:25–33 [Google Scholar]
  160. Macatonia SE, Cruickshank JK, Rudge P, Knight SC. 160.  1992. Dendritic cells from patients with tropical spastic paraparesis are infected with HTLV-1 and stimulate autologous lymphocyte proliferation. AIDS Res. Hum. Retrovir. 8:1699–706 [Google Scholar]
  161. Ando S, Hasegawa A, Murakami Y, Zeng N, Takatsuka N. 161.  et al. 2017. HTLV-1 Tax-specific CTL epitope-pulsed dendritic cell therapy reduces proviral load in infected rats with immune tolerance against Tax. J. Immunol. 198:1210–19 [Google Scholar]
  162. Suehiro Y, Hasegawa A, Iino T, Sasada A, Watanabe N. 162.  et al. 2015. Clinical outcomes of a novel therapeutic vaccine with Tax peptide-pulsed dendritic cells for adult T cell leukaemia/lymphoma in a pilot study. Br. J. Haematol. 169:356–67 [Google Scholar]
  163. Kinpara S, Hasegawa A, Utsunomiya A, Nishitsuji H, Furukawa H. 163.  et al. 2009. Stromal cell-mediated suppression of human T-cell leukemia virus type 1 expression in vitro and in vivo by type I interferon. J. Virol. 83:5101–8 [Google Scholar]
  164. Yuen CK, Chan CP, Fung SY, Wang PH, Wong WM. 164.  et al. 2016. Suppression of type I interferon production by human T-cell leukemia virus type 1 oncoprotein Tax through inhibition of IRF3 phosphorylation. J. Virol. 90:3902–12 [Google Scholar]
  165. Dassouki Z, Sahin U, El Hajj H, Jollivet F, Kfoury Y. 165.  et al. 2015. ATL response to arsenic/interferon therapy is triggered by SUMO/PML/RNF4-dependent Tax degradation. Blood 125:474–82 [Google Scholar]
  166. Seich al Basatena NK, MacNamara A, Vine AM, Thio CL, Astemborski J. 166.  et al. 2011. KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection. PLOS Pathog 7:e1002270 [Google Scholar]
  167. Goon PK, Biancardi A, Fast N, Igakura T, Hanon E. 167.  et al. 2004. Human T cell lymphotropic virus (HTLV) type-1-specific CD8+ T cells: frequency and immunodominance hierarchy. J. Infect. Dis. 189:2294–98 [Google Scholar]
  168. Kannagi M, Harada S, Maruyama I, Inoko H, Igarashi H. 168.  et al. 1991. Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells. Int. Immunol. 3:761–67 [Google Scholar]
  169. Jacobson S, Shida H, McFarlin DE, Fauci AS, Koenig S. 169.  1990. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature 348:245–48 [Google Scholar]
  170. Nowak MA, Bangham CR. 170.  1996. Population dynamics of immune responses to persistent viruses. Science 272:74–79 [Google Scholar]
  171. Jeffery KJ, Usuku K, Hall SE, Matsumoto W, Taylor GP. 171.  et al. 1999. HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. PNAS 96:3848–53 [Google Scholar]
  172. Rende F, Cavallari I, Corradin A, Silic-Benussi M, Toulza F. 172.  et al. 2011. Kinetics and intracellular compartmentalization of HTLV-1 gene expression: nuclear retention of HBZ mRNAs. Blood 117:4855–59 [Google Scholar]
  173. Goon PK, Hanon E, Igakura T, Tanaka Y, Weber JN. 173.  et al. 2002. 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 99:3335–41 [Google Scholar]
  174. Karube K, Aoki R, Sugita Y, Yoshida S, Nomura Y. 174.  et al. 2008. The relationship of FOXP3 expression and clinicopathological characteristics in adult T-cell leukemia/lymphoma. Mod. Pathol. 21:617–25 [Google Scholar]
  175. Waldmann TA, Greene WC, Sarin PS, Saxinger C, Blayney DW. 175.  et al. 1984. Functional and phenotypic comparison of human T cell leukemia/lymphoma virus positive adult T cell leukemia with human T cell leukemia/lymphoma virus negative Sézary leukemia, and their distinction using anti-Tac. Monoclonal antibody identifying the human receptor for T cell growth factor. J. Clin. Investig. 73:1711–18 [Google Scholar]
  176. Toulza F, Heaps A, Tanaka Y, Taylor GP, Bangham CR. 176.  2008. High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1-specific CTL response. Blood 111:5047–53 [Google Scholar]
  177. Toulza F, Nosaka K, Takiguchi M, Pagliuca T, Mitsuya H. 177.  et al. 2009. FoxP3+ regulatory T cells are distinct from leukemia cells in HTLV-1-associated adult T-cell leukemia. Int. J. Cancer 125:2375–82 [Google Scholar]
  178. Bangham CR, Toulza F. 178.  2011. Adult T cell leukemia/lymphoma: FoxP3+ cells and the cell-mediated immune response to HTLV-1. Adv. Cancer Res. 111:163–82 [Google Scholar]
  179. Hieshima K, Nagakubo D, Nakayama T, Shirakawa AK, Jin Z, Yoshie O. 179.  2008. Tax-inducible production of CC chemokine ligand 22 by human T cell leukemia virus type 1 (HTLV-1)-infected T cells promotes preferential transmission of HTLV-1 to CCR4-expressing CD4+ T cells. J. Immunol. 180:931–39 [Google Scholar]
  180. Lenstra TL, Rodriguez J, Chen H, Larson DR. 180.  2016. Transcription dynamics in living cells. Annu. Rev. Biophys. 45:25–47 [Google Scholar]
  181. Billman MR, Rueda D, Bangham CRM. 181.  2017. Single-cell heterogeneity and cell-cycle-related viral gene bursts in the human leukaemia virus HTLV-1. Wellcome Open Res 2:87 [Google Scholar]
  182. Kulkarni A, Mateus M, Thinnes CC, McCullagh JS, Schofield CJ. 182.  et al. 2017. Glucose metabolism and oxygen availability govern reactivation of the latent human retrovirus HTLV-1. Cell Chem. Biol. 24:1377–87 [Google Scholar]
  183. Satou Y, Miyazato P, Ishihara K, Yaguchi H, Melamed A. 183.  et al. 2016. The retrovirus HTLV-1 inserts an ectopic CTCF-binding site into the human genome. PNAS 113:3054–59 [Google Scholar]
  184. Phillips JE, Corces VG. 184.  2009. CTCF: master weaver of the genome. Cell 137:1194–211 [Google Scholar]
  185. Nora EP, Goloborodko A, Valton AL, Gibcus JH, Uebersohn A. 185.  et al. 2017. Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization. Cell 169:930–44.e22 [Google Scholar]
  186. Busslinger GA, Stocsits RR, van der Lelij P, Axelsson E, Tedeschi A. 186.  et al. 2017. Cohesin is positioned in mammalian genomes by transcription, CTCF and Wapl. Nature 544:503–7 [Google Scholar]
  187. Parelho V, Hadjur S, Spivakov M, Leleu M, Sauer S. 187.  et al. 2008. Cohesins functionally associate with CTCF on mammalian chromosome arms. Cell 132:422–33 [Google Scholar]
  188. Wendt KS, Yoshida K, Itoh T, Bando M, Koch B. 188.  et al. 2008. Cohesin mediates transcriptional insulation by CCCTC-binding factor. Nature 451:796–801 [Google Scholar]
  189. Hickey WF, Hsu BL, Kimura H. 189.  1991. Lymphocyte-T entry into the central-nervous-system. J. Neurosci. Res. 28:254–60 [Google Scholar]
  190. Wekerle H, Linington C, Lassmann H, Meyermann R. 190.  1986. Cellular immune reactivity within the CNS. Trends Neurosci 9:271–77 [Google Scholar]
  191. Bradl M, Bauer J, Flugel A, Wekerle H, Lassmann H. 191.  2005. Complementary contribution of CD4 and CD8 T lymphocytes to T-cell infiltration of the intact and the degenerative spinal cord. Am. J. Pathol. 166:1441–50 [Google Scholar]
  192. Curis C, Percher F, Jeannin P, Montange T, Chevalier SA. 192.  et al. 2016. Human T-lymphotropic virus type 1-induced overexpression of activated leukocyte cell adhesion molecule (ALCAM) facilitates trafficking of infected lymphocytes through the blood-brain barrier. J. Virol. 90:7303–12 [Google Scholar]
  193. Dimber R, Guo Q, Bishop C, Adonis A, Buckley A. 193.  et al. 2016. Evidence of brain inflammation in patients with human T-lymphotropic virus type 1-associated myelopathy (HAM): a pilot, multimodal imaging study using 11C-PBR28 PET, MR T1-weighted, and diffusion-weighted imaging. J. Nucl. Med. 57:1905–12 [Google Scholar]
  194. Jacobson S. 194.  2002. Immunopathogenesis of human T cell lymphotropic virus type I–associated neurologic disease. J. Infect. Dis. 186:Suppl. 2S187–92 [Google Scholar]
  195. Levin MC, Lee SM, Kalume F, Morcos Y, Dohan FC Jr.. 195.  et al. 2002. Autoimmunity due to molecular mimicry as a cause of neurological disease. Nat. Med. 8:509–13 [Google Scholar]
  196. Yukitake M, Sueoka E, Sueoka-Aragane N, Sato A, Ohashi H. 196.  et al. 2008. Significantly increased antibody response to heterogeneous nuclear ribonucleoproteins in cerebrospinal fluid of multiple sclerosis patients but not in patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J. Neurovirol. 14:130–35 [Google Scholar]
  197. Daenke S, Bangham CR. 197.  1994. Do T cells cause HTLV-1-associated disease? A taxing problem. Clin. Exp. Immunol. 96:179–81 [Google Scholar]
  198. Ijichi S, Izumo S, Eiraku N, Machigashira K, Kubota R. 198.  et al. 1993. An autoaggressive process against bystander tissues in HTLV-I-infected individuals: a possible pathomechanism of HAM/TSP. Med. Hypotheses 41:542–47 [Google Scholar]
  199. Alexander WS, Starr R, Fenner JE, Scott CL, Handman E. 199.  et al. 1999. SOCS1 is a critical inhibitor of interferon gamma signaling and prevents the potentially fatal neonatal actions of this cytokine. Cell 98:597–608 [Google Scholar]
  200. Marine JC, Topham DJ, McKay C, Wang D, Parganas E. 200.  et al. 1999. SOCS1 deficiency causes a lymphocyte-dependent perinatal lethality. Cell 98:609–16 [Google Scholar]
  201. Schroder K, Hertzog PJ, Ravasi T, Hume DA. 201.  2004. Interferon-gamma: an overview of signals, mechanisms and functions. J. Leukoc. Biol. 75:163–89 [Google Scholar]
  202. Hanon E, Goon P, Taylor GP, Hasegawa H, Tanaka Y. 202.  et al. 2001. High production of interferon gamma but not interleukin-2 by human T-lymphotropic virus type I-infected peripheral blood mononuclear cells. Blood 98:721–26 [Google Scholar]
  203. Hashioka S, Klegeris A, Schwab C, Yu S, McGeer PL. 203.  2010. Differential expression of interferon-gamma receptor on human glial cells in vivo and in vitro. J. Neuroimmunol. 225:91–99 [Google Scholar]
  204. Ando H, Sato T, Tomaru U, Yoshida M, Utsunomiya A. 204.  et al. 2013. Positive feedback loop via astrocytes causes chronic inflammation in virus-associated myelopathy. Brain 136:2876–87 [Google Scholar]
  205. Kunis G, Baruch K, Rosenzweig N, Kertser A, Miller O. 205.  et al. 2013. IFN-gamma-dependent activation of the brain's choroid plexus for CNS immune surveillance and repair. Brain 136:3427–40 [Google Scholar]
  206. Deczkowska A, Baruch K, Schwartz M. 206.  2016. Type I/II interferon balance in the regulation of brain physiology and pathology. Trends Immunol 37:181–92 [Google Scholar]
  207. Tattermusch S, Skinner JA, Chaussabel D, Banchereau J, Berry MP. 207.  et al. 2012. Systems biology approaches reveal a specific IFN-inducible signature in HTLV-1 associated myelopathy. PLOS Pathog 8:e1002480 [Google Scholar]
  208. da Silva Dias GA, Sousa RC, Gomes LF, Caldas CA, Nassiri R. 208.  et al. 2016. Correlation between clinical symptoms and peripheral immune response in HAM/TSP. Microb. Pathog. 92:72–75 [Google Scholar]
  209. Espindola OM, Oliveira LC, Ferreira PM, Leite AC, Lima MA, Andrada-Serpa MJ. 209.  2015. High IFN-gamma/IL-10 expression ratio and increased frequency of persistent human T-cell lymphotropic virus type 1-infected clones are associated with human T-cell lymphotropic virus type 1-associated myelopathy/tropical spastic paraparesis development. Intervirology 58:106–14 [Google Scholar]
  210. Montanheiro PA, Penalva de Oliveira AC, Smid J, Fukumori LM, Olah I. 210.  et al. 2009. The elevated interferon gamma production is an important immunological marker in HAM/TSP pathogenesis. Scand. J. Immunol. 70:403–7 [Google Scholar]
  211. Lima CM, Santos S, Dourado A, Carvalho NB, Bittencourt V. 211.  et al. 2016. association of sicca syndrome with proviral load and proinflammatory cytokines in HTLV-1 infection. J. Immunol. Res. 2016:8402059 [Google Scholar]
  212. Mitagami Y, Yasunaga J, Kinosada H, Ohshima K, Matsuoka M. 212.  2015. Interferon-gamma promotes inflammation and development of T-Cell lymphoma in HTLV-1 bZIP factor transgenic mice. PLOS Pathog 11:e1005120 [Google Scholar]
  213. Araujo AQ. 213.  2015. Update on neurological manifestations of HTLV-1 infection. Curr. Infect. Dis. Rep. 17:459 [Google Scholar]
  214. Tanajura D, Castro N, Oliveira P, Neto A, Muniz A. 214.  et al. 2015. Neurological manifestations in human T-cell lymphotropic virus type 1 (HTLV-1)-infected individuals without HTLV-1-associated myelopathy/tropical spastic paraparesis: a longitudinal cohort study. Clin. Infect. Dis. 61:49–56 [Google Scholar]
  215. Sugata K, Yasunaga J, Miura M, Akari H, Utsunomiya A. 215.  et al. 2016. Enhancement of anti-STLV-1/HTLV-1 immune responses through multimodal effects of anti-CCR4 antibody. Sci. Rep. 6:27150 [Google Scholar]
  216. Tsukasaki K, Tobinai K. 216.  2013. Biology and treatment of HTLV-1 associated T-cell lymphomas. Best Pract. Res. Clin. Haematol. 26:3–14 [Google Scholar]
  217. Yasunaga J, Matsuoka M. 217.  2011. Molecular mechanisms of HTLV-1 infection and pathogenesis. Int. J. Hematol. 94:435–42 [Google Scholar]
  218. Okamoto T, Ohno Y, Tsugane S, Watanabe S, Shimoyama M. 218.  et al. 1989. Multi-step carcinogenesis model for adult T-cell leukemia. Jpn. J. Cancer Res. 80:191–95 [Google Scholar]
  219. Aoki S, Firouzi S, Lopez Y, Yamochi T, Nakano K. 219.  et al. 2016. Transition of adult T-cell leukemia/lymphoma clones during clinical progression. Int. J. Hematol. 104:330–37 [Google Scholar]
  220. Furukawa Y, Tara M, Niina K, Kubo H, Imaguma M. 220.  1993. Clonal change of HTLV-1 infected lymphocytes before onset of adult T-cell leukemia/lymphoma [in Japanese]. Rinsho Ketsueki 34:967–69 [Google Scholar]
  221. Iwatsuki K, Inoue F, Takigawa M, Iemoto G, Nagatani T. 221.  et al. 1990. Exchange of dominant lymphoid cell clones in a patient with adult T-cell leukemia/lymphoma. Acta Derm. Venereol. 70:49–52 [Google Scholar]
  222. Tsukasaki K, Tsushima H, Yamamura M, Hata T, Murata K. 222.  et al. 1997. Integration patterns of HTLV-I provirus in relation to the clinical course of ATL: frequent clonal change at crisis from indolent disease. Blood 89:948–56 [Google Scholar]
  223. Miura M, Yasunaga J, Tanabe J, Sugata K, Zhao T. 223.  et al. 2013. Characterization of simian T-cell leukemia virus type 1 in naturally infected Japanese macaques as a model of HTLV-1 infection. Retrovirology 10:118 [Google Scholar]
  224. Turpin J, Alais S, Marcais A, Bruneau J, Melamed A. 224.  et al. 2017. Whole body clonality analysis in an aggressive STLV-1 associated leukemia (ATLL) reveals an unexpected clonal complexity. Cancer Lett 389:78–85 [Google Scholar]
  225. Villaudy J, Wencker M, Gadot N, Scoazec J-Y, Gazzolo L. 225.  et al. 2011. HTLV-1 propels thymic human T cell development in “human immune system” Rag2−/− IL-2R gamma c−/− mice. PLOS Pathog 7:e1002231 [Google Scholar]
  226. Tomasetti C, Vogelstein B. 226.  2015. Cancer etiology: Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347:78–81 [Google Scholar]
  227. Sakashita A, Hattori T, Miller CW, Suzushima H, Asou N. 227.  et al. 1992. Mutations of the p53 gene in adult T-cell leukemia. Blood 79:477–80 [Google Scholar]
  228. Nagata Y, Kontani K, Enami T, Kataoka K, Ishii R. 228.  et al. 2016. Variegated RHOA mutations in adult T-cell leukemia/lymphoma. Blood 127:596–604 [Google Scholar]
  229. Yeh CH, Bellon M, Pancewicz-Wojtkiewicz J, Nicot C. 229.  2016. Oncogenic mutations in the FBXW7 gene of adult T-cell leukemia patients. PNAS 113:6731–36 [Google Scholar]
  230. Fujikawa D, Nakagawa S, Hori M, Kurokawa N, Soejima A. 230.  et al. 2016. Polycomb-dependent epigenetic landscape in adult T-cell leukemia. Blood 127:1790–802 [Google Scholar]
  231. Yamagishi M, Nakano K, Miyake A, Yamochi T, Kagami Y. 231.  et al. 2012. Polycomb-mediated loss of miR-31 activates NIK-dependent NF-κB pathway in adult T cell leukemia and other cancers. Cancer Cell 21:121–35 [Google Scholar]
  232. Asquith B, Zhang Y, Mosley AJ, de Lara CM, Wallace DL. 232.  et al. 2007. In vivo T lymphocyte dynamics in humans and the impact of human T lymphotropic virus 1 infection. PNAS 104:8035–40 [Google Scholar]
  233. Rowan AG, Witkover A, Melamed A, Tanaka Y, Cook LB. 233.  et al. 2016. T cell receptor Vβ staining identifies the malignant clone in adult T cell leukemia and reveals killing of leukemia cells by autologous CD8+ T cells. PLOS Pathog 12:e1006030 [Google Scholar]
  234. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N. 234.  et al. 1998. 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. 4:586–93 [Google Scholar]
  235. Kubota R, Fujiyoshi T, Izumo S, Yashiki S, Maruyama I. 235.  et al. 1993. Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy. J. Neuroimmunol. 42:147–54 [Google Scholar]
  236. Kwaan N, Lee TH, Chafets DM, Nass C, Newman B. 236.  et al. 2006. Long-term variations in human T lymphotropic virus (HTLV)-I and HTLV-II proviral loads and association with clinical data. J. Infect. Dis. 194:1557–64 [Google Scholar]
  237. Bangham CRM, Matsuoka M. 237.  2017. Human T-cell leukemia virus type 1: parasitism and pathogenesis. Phil. Trans. R. Soc. B. 372:20160272 [Google Scholar]
/content/journals/10.1146/annurev-immunol-042617-053222
Loading
Human T Cell Leukemia Virus Type 1: Persistence and Pathogenesis
Annual Review of Immunology 36, 43 (2018); https://doi.org/10.1146/annurev-immunol-042617-053222
/content/journals/10.1146/annurev-immunol-042617-053222
/content/journals/10.1146/annurev-immunol-042617-053222
Loading

Data & Media loading...

  • Article Type: Review Article

Most Cited 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