Journal of NeuroVirology

, Volume 22, Issue 4, pp 416–430 | Cite as

HTLV-1 subgroups associated with the risk of HAM/TSP are related to viral and host gene expression in peripheral blood mononuclear cells, independent of the transactivation functions of the viral factors

  • Keiko Yasuma
  • Toshio Matsuzaki
  • Yoshihisa Yamano
  • Hiroshi Takashima
  • Masao Matsuoka
  • Mineki Saito


Among human T cell leukemia virus type 1 (HTLV-1)-infected individuals, the risk of developing HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) across lifetime differs between ethnic groups. There is an association between HTLV-1 tax gene subgroups (subgroup-A or subgroup-B) and the risk of HAM/TSP in the Japanese population. In this study, we investigated the full-length proviral genome sequences of various HTLV-1-infected cell lines and patient samples. The functional differences in the viral transcriptional regulators Tax and HTLV-1 bZIP factor (HBZ) between each subgroup and the relationships between subgroups and the clinical and laboratory characteristics of HAM/TSP patients were evaluated. The results of these analyses indicated the following: (1) distinct nucleotide substitutions corresponding to each subgroup were associated with nucleotide substitutions in viral structural, regulatory, and accessory genes; (2) the HBZ messenger RNA (mRNA) expression in HTLV-1-infected cells was significantly higher in HAM/TSP patients with subgroup-B than in those with subgroup-A; (3) a positive correlation was observed between the expression of HBZ mRNA and its target Foxp3 mRNA in HAM/TSP patients with subgroup-B, but not in patients with subgroup-A; (4) no clear differences were noted in clinical and laboratory characteristics between HAM/TSP patients with subgroup-A and subgroup-B; and (5) no functional differences were observed in Tax and HBZ between each subgroup based on reporter gene assays. Our results indicate that although different HTLV-1 subgroups are characterized by different patterns of viral and host gene expression in HAM/TSP patients via independent mechanisms of direct transcriptional regulation, these differences do not significantly affect the clinical and laboratory characteristics of HAM/TSP patients.


HTLV-1 Virus subgroup HAM/TSP Tax HBZ Foxp3 



This work was supported by KAKENHI from the Japan Society for the Promotion of Science (JSPS) (Grant Numbers 21590512, 24590556, and 15K09345); the Health and Labor Sciences Research Grants (research on rare and intractable diseases, Grant Numbers H22-013, H23-126, H25-023, and H25-028); the Japan Agency for Medical Research and Development (AMED); the Project of Establishing Medical Research Base Networks Against Infectious Diseases in Okinawa; the Novartis Foundation for the Promotion of Science (Japan); and the Joint Usage/Research Center Program of the Institute for Virus Research, Kyoto University.

Compliance with ethical standards

The Institutional Review Boards of the authors’ institutions approved this research and written informed consent was obtained from all study participants.

Conflict of interest

The authors declare that they have no competing interests.

Supplementary material

13365_2015_407_MOESM1_ESM.pptx (179 kb)
Supplementary Figure 1 Subgroup specific tax nucleotide substitutions are linked with those of viral structural, regulatory, and accessory HTLV-1 genes. Nucleotide substitutions of tax subgroups (subgroup-A or subgroup-B) are linked with nucleotide substitutions of LTR, p12, p30, envelope (env), the gal/pol precursor, and HBZ HTLV-1 genes. A. Nucleotide substitutions in the viral long terminal repeat (LTR). B. Amino acid substitution in the HTLV-1 accessory protein p12. C. Amino acid substitutions in the HTLV-1 accessory protein p30. D. Amino acid substitutions in the HTLV-1 structural protein Env. E. Amino acid substitution in the gag/pol precursor. F. Amino acid substitution in the HBZ. (PPTX 179 kb)
13365_2015_407_MOESM2_ESM.docx (17 kb)
Supplementary Table 1 Osame Motor Disability Score (OMDS) for evaluation of motor dysfunction in HAM/TSP patents. (DOCX 16 kb)


  1. Albrecht B, Collins ND, Burniston MT, Nisbet JW, Ratner L, Green PL, Lairmore MD (2000) Human T-lymphotropic virus type 1 open reading frame I p12(I) is required for efficient viral infectivity in primary lymphocytes. J Virol 74:9828–35CrossRefPubMedPubMedCentralGoogle Scholar
  2. Anderson MR, Enose-Akahata Y, Massoud R, Ngouth N, Tanaka Y, Oh U, Jacobson S (2014) Epigenetic modification of the FoxP3 TSDR in HAM/TSP decreases the functional suppression of Tregs. J Neuroimmune Pharmacol 9:522–32CrossRefPubMedPubMedCentralGoogle Scholar
  3. Arnulf B, Villemain A, Nicot C, Mordelet E, Charneau P, Kersual J, Zermati Y, Mauviel A, Bazarbachi A, Hermine O (2002) 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 100:4129–38CrossRefPubMedGoogle Scholar
  4. Brady J, Jeang KT, Duvall J, Khoury G (1987) Identification of p40x-responsive regulatory sequences within the human T-cell leukemia virus type I long terminal repeat. J Virol 61:2175–81PubMedPubMedCentralGoogle Scholar
  5. Cavanagh MH, Landry S, Audet B, Arpin-Andre C, Hivin P, Pare ME, Thete J, Wattel E, Marriott SJ, Mesnard JM, Barbeau B (2006) HTLV-I antisense transcripts initiating in the 3′LTR are alternatively spliced and polyadenylated. Retrovirology 3:15CrossRefPubMedPubMedCentralGoogle Scholar
  6. de The G, Bomford R (1993) An HTLV-I vaccine: why, how, for whom? AIDS Res Hum Retrovir 9:381–6CrossRefPubMedGoogle Scholar
  7. Fan J, Ma G, Nosaka K, Tanabe J, Satou Y, Koito A, Wain-Hobson S, Vartanian JP, Matsuoka M (2010) APOBEC3G generates nonsense mutations in human T-cell leukemia virus type 1 proviral genomes in vivo. J Virol 84:7278–87CrossRefPubMedPubMedCentralGoogle Scholar
  8. Fu W, Shah SR, Jiang H, Hilt DC, Dave HP, Joshi JB (1997) Transactivation of proenkephalin gene by HTLV-1 tax1 protein in glial cells: involvement of Fos/Jun complex at an AP-1 element in the proenkephalin gene promoter. J Neurovirol 3:16–27CrossRefPubMedGoogle Scholar
  9. Fujisawa J, Toita M, Yoshida M (1989) A unique enhancer element for the trans activator (p40tax) of human T-cell leukemia virus type I that is distinct from cyclic AMP- and 12-O-tetradecanoylphorbol-13-acetate-responsive elements. J Virol 63:3234–9PubMedPubMedCentralGoogle Scholar
  10. Furukawa Y, Yamashita M, Usuku K, Izumo S, Nakagawa M, Osame M (2000) Phylogenetic subgroups of human T cell lymphotropic virus (HTLV) type I in the tax gene and their association with different risks for HTLV-I-associated myelopathy/tropical spastic paraparesis. J Infect Dis 182:1343–9CrossRefPubMedGoogle Scholar
  11. Gessain A, Barin F, Vernant JC, Gout O, Maurs L, Calender A, de The G (1985) Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet 2:407–10CrossRefPubMedGoogle Scholar
  12. Hayashi D, Kubota R, Takenouchi N, Nakamura T, Umehara F, Arimura K, Izumo S, Osame M (2008) Accumulation of human T-lymphotropic virus type I (HTLV-I)-infected cells in the cerebrospinal fluid during the exacerbation of HTLV-I-associated myelopathy. J Neurovirol 14:459–63CrossRefPubMedGoogle Scholar
  13. Hisada M, Stuver SO, Okayama A, Li HC, Sawada T, Hanchard B, Mueller NE (2004) Persistent paradox of natural history of human T lymphotropic virus type I: parallel analyses of Japanese and Jamaican carriers. J Infect Dis 190:1605–9CrossRefPubMedGoogle Scholar
  14. Huehn J, Polansky JK, Hamann A (2009) Epigenetic control of FOXP3 expression: the key to a stable regulatory T-cell lineage? Nat Rev Immunol 9:83–9CrossRefPubMedGoogle Scholar
  15. Iwai K, Mori N, Oie M, Yamamoto N, Fujii M (2001) Human T-cell leukemia virus type 1 tax protein activates transcription through AP-1 site by inducing DNA binding activity in T cells. Virology 279:38–46CrossRefPubMedGoogle Scholar
  16. Izumo S, Goto I, Itoyama Y, Okajima T, Watanabe S, Kuroda Y, Araki S, Mori M, Nagataki S, Matsukura S, Akamine T, Nakagawa M, Yamamoto I, Osame M (1996) Interferon-alpha is effective in HTLV-I-associated myelopathy: a multicenter, randomized, double-blind, controlled trial. Neurology 46:1016–21CrossRefPubMedGoogle Scholar
  17. John-Stewart GC, Nduati RW, Rousseau CM, Mbori-Ngacha DA, Richardson BA, Rainwater S, Panteleeff DD, Overbaugh J (2005) Subtype C is associated with increased vaginal shedding of HIV-1. J Infect Dis 192:492–6CrossRefPubMedPubMedCentralGoogle Scholar
  18. Keller M, Lu Y, Lalonde RG, Klein MB (2009) Impact of HIV-1 viral subtype on CD4+ T-cell decline and clinical outcomes in antiretroviral naive patients receiving universal healthcare. AIDS 23:731–7PubMedGoogle Scholar
  19. Kiwanuka N, Laeyendecker O, Quinn TC, Wawer MJ, Shepherd J, Robb M, Kigozi G, Kagaayi J, Serwadda D, Makumbi FE, Reynolds SJ, Gray RH (2009) HIV-1 subtypes and differences in heterosexual HIV transmission among HIV-discordant couples in Rakai, Uganda. AIDS 23:2479–84CrossRefPubMedPubMedCentralGoogle Scholar
  20. Kiwanuka N, Robb M, Laeyendecker O, Kigozi G, Wabwire-Mangen F, Makumbi FE, Nalugoda F, Kagaayi J, Eller M, Eller LA, Serwadda D, Sewankambo NK, Reynolds SJ, Quinn TC, Gray RH, Wawer MJ, Whalen CC (2010) HIV-1 viral subtype differences in the rate of CD4+ T-cell decline among HIV seroincident antiretroviral naive persons in Rakai district, Uganda. J Acquir Immune Defic Syndr 54:180–4PubMedPubMedCentralGoogle Scholar
  21. Kohli A, Shaffer A, Sherman A, Kottilil S (2014) Treatment of hepatitis C: a systematic review. JAMA 312:631–40CrossRefPubMedGoogle Scholar
  22. Kramer A, Maloney EM, Morgan OS, Rodgers-Johnson P, Manns A, Murphy EL, Larsen S, Cranston B, Murphy J, Benichou J et al (1995) Risk factors and cofactors for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) in Jamaica. Am J Epidemiol 142:1212–20PubMedGoogle Scholar
  23. Kuo CW, Mirsaliotis A, Brighty DW (2011) Antibodies to the envelope glycoprotein of human T cell leukemia virus type 1 robustly activate cell-mediated cytotoxic responses and directly neutralize viral infectivity at multiple steps of the entry process. J Immunol 187:361–71CrossRefPubMedGoogle Scholar
  24. Lee DK, Kim BC, Brady JN, Jeang KT, Kim SJ (2002) Human T-cell lymphotropic virus type 1 tax inhibits transforming growth factor-beta signaling by blocking the association of Smad proteins with Smad-binding element. J Biol Chem 277:33766–75CrossRefPubMedGoogle Scholar
  25. Ma G, Yasunaga J, Fan J, Yanagawa S, Matsuoka M (2013) HTLV-1 bZIP factor dysregulates the Wnt pathways to support proliferation and migration of adult T-cell leukemia cells. Oncogene 32:4222–30CrossRefPubMedGoogle Scholar
  26. Maeda Y, Terasawa H, Tanaka Y, Mitsuura C, Nakashima K, Yusa K, Harada S (2015) Separate cellular localizations of human T-lymphotropic virus 1 (HTLV-1) Env and glucose transporter type 1 (GLUT1) are required for HTLV-1 Env-mediated fusion and infection. J Virol 89:502–11CrossRefPubMedGoogle Scholar
  27. Manel N, Taylor N, Kinet S, Kim FJ, Swainson L, Lavanya M, Battini JL, Sitbon M (2004) HTLV envelopes and their receptor GLUT1, the ubiquitous glucose transporter: a new vision on HTLV infection? Front Biosci 9:3218–41CrossRefPubMedGoogle Scholar
  28. Matsumoto J, Ohshima T, Isono O, Shimotohno K (2005) HTLV-1 HBZ suppresses AP-1 activity by impairing both the DNA-binding ability and the stability of c-Jun protein. Oncogene 24:1001–10CrossRefPubMedGoogle Scholar
  29. Matsuoka M (2010) HTLV-1 bZIP factor gene: its roles in HTLV-1 pathogenesis. Mol Asp Med 31:359–66CrossRefGoogle Scholar
  30. Miyazato P, Matsuoka M (2014) Human T-cell leukemia virus type 1 and Foxp3 expression: viral strategy in vivo. Int Immunol 26:419–425CrossRefPubMedGoogle Scholar
  31. Morgan ME, van Bilsen JH, Bakker AM, Heemskerk B, Schilham MW, Hartgers FC, Elferink BG, van der Zanden L, de Vries RR, Huizinga TW, Ottenhoff TH, Toes RE (2005) Expression of FOXP3 mRNA is not confined to CD4+CD25+ T regulatory cells in humans. Hum Immunol 66:13–20CrossRefPubMedGoogle Scholar
  32. Murata K, Hayashibara T, Sugahara K, Uemura A, Yamaguchi T, Harasawa H, Hasegawa H, Tsuruda K, Okazaki T, Koji T, Miyanishi T, Yamada Y, Kamihira S (2006) A novel alternative splicing isoform of human T-cell leukemia virus type 1 bZIP factor (HBZ-SI) targets distinct subnuclear localization. J Virol 80:2495–505CrossRefPubMedPubMedCentralGoogle Scholar
  33. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N, Moritoyo T, Hashiguchi S, Ichinose M, Bangham CR, Izumo S, Osame M (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 4:586–93CrossRefPubMedGoogle Scholar
  34. Nakagawa M, Izumo S, Ijichi S, Kubota H, Arimura K, Kawabata M, Osame M (1995) HTLV-I-associated myelopathy: analysis of 213 patients based on clinical features and laboratory findings. J Neurovirol 1:50–61CrossRefPubMedGoogle Scholar
  35. Nicot C, Mulloy JC, Ferrari MG, Johnson JM, Fu K, Fukumoto R, Trovato R, Fullen J, Leonard WJ, Franchini G (2001) HTLV-1 p12(I) protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells. Blood 98:823–9CrossRefPubMedGoogle Scholar
  36. Nicot C, Dundr M, Johnson JM, Fullen JR, Alonzo N, Fukumoto R, Princler GL, Derse D, Misteli T, Franchini G (2004) HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication. Nat Med 10:197–201CrossRefPubMedGoogle Scholar
  37. Oh SA, Li MO (2013) TGF-beta: guardian of T cell function. J Immunol 191:3973–9CrossRefPubMedPubMedCentralGoogle Scholar
  38. Osame M (1990) Review of WHO Kagoshima meeting and diagnostic guidelines for HAM/TSP. Raven, New YorkGoogle Scholar
  39. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H, Igata A, Matsumoto M, Tara M (1986) HTLV-I associated myelopathy, a new clinical entity. Lancet 1:1031–2CrossRefPubMedGoogle Scholar
  40. Osame M, Janssen R, Kubota H, Nishitani H, Igata A, Nagataki S, Mori M, Goto I, Shimabukuro H, Khabbaz R et al (1990) Nationwide survey of HTLV-I-associated myelopathy in Japan: association with blood transfusion. Ann Neurol 28:50–6CrossRefPubMedGoogle Scholar
  41. Proietti FA, Carneiro-Proietti AB, Catalan-Soares BC, Murphy EL (2005) Global epidemiology of HTLV-I infection and associated diseases. Oncogene 24:6058–68CrossRefPubMedGoogle Scholar
  42. Sabouri AH, Saito M, Usuku K, Bajestan SN, Mahmoudi M, Forughipour M, Sabouri Z, Abbaspour Z, Goharjoo ME, Khayami E, Hasani A, Izumo S, Arimura K, Farid R, Osame M (2005) Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals. J Gen Virol 86:773–81CrossRefPubMedGoogle Scholar
  43. Saito M, Nakagawa M, Kaseda S, Matsuzaki T, Jonosono M, Eiraku N, Kubota R, Takenouchi N, Nagai M, Furukawa Y, Usuku K, Izumo S, Osame M (2004) Decreased human T lymphotropic virus type I (HTLV-I) provirus load and alteration in T cell phenotype after interferon-alpha therapy for HTLV-I-associated myelopathy/tropical spastic paraparesis. J Infect Dis 189:29–40CrossRefPubMedGoogle Scholar
  44. Saito M, Matsuzaki T, Satou Y, Yasunaga J, Saito K, Arimura K, Matsuoka M, Ohara Y (2009) In vivo expression of the HBZ gene of HTLV-1 correlates with proviral load, inflammatory markers and disease severity in HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP). Retrovirology 6:19CrossRefPubMedPubMedCentralGoogle Scholar
  45. Satou Y, Yasunaga J, Yoshida M, Matsuoka M (2006) HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells. Proc Natl Acad Sci U S A 103:720–5CrossRefPubMedPubMedCentralGoogle Scholar
  46. Satou Y, Yasunaga J, Zhao T, Yoshida M, Miyazato P, Takai K, Shimizu K, Ohshima K, Green PL, Ohkura N, Yamaguchi T, Ono M, Sakaguchi S, Matsuoka M (2011) HTLV-1 bZIP factor induces T-cell lymphoma and systemic inflammation in vivo. PLoS Pathog 7:e1001274CrossRefPubMedPubMedCentralGoogle Scholar
  47. Seiki M, Hattori S, Hirayama Y, Yoshida M (1983) Human adult T-cell leukemia virus: complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA. Proc Natl Acad Sci U S A 80:3618–22CrossRefPubMedPubMedCentralGoogle Scholar
  48. Sugata K, Satou Y, Yasunaga J, Hara H, Ohshima K, Utsunomiya A, Mitsuyama M, Matsuoka M (2012) HTLV-1 bZIP factor impairs cell-mediated immunity by suppressing production of Th1 cytokines. Blood 119:434–44CrossRefPubMedPubMedCentralGoogle Scholar
  49. Tajima K (1990) The 4th nation-wide study of adult T-cell leukemia/lymphoma (ATL) in Japan: estimates of risk of ATL and its geographical and clinical features. The T- and B-cell Malignancy Study Group. Int J Cancer 45:237–43CrossRefPubMedGoogle Scholar
  50. Tanaka M, Herr W (1990) Differential transcriptional activation by Oct-1 and Oct-2: interdependent activation domains induce Oct-2 phosphorylation. Cell 60:375–86CrossRefPubMedGoogle Scholar
  51. Taylor JM, Brown M, Nejmeddine M, Kim KJ, Ratner L, Lairmore M, Nicot C (2009) Novel role for interleukin-2 receptor-Jak signaling in retrovirus transmission. J Virol 83:11467–76CrossRefPubMedPubMedCentralGoogle Scholar
  52. Thomas M, Narayan N, Pim D, Tomaic V, Massimi P, Nagasaka K, Kranjec C, Gammoh N, Banks L (2008) Human papillomaviruses, cervical cancer and cell polarity. Oncogene 27:7018–30CrossRefPubMedGoogle Scholar
  53. Tone Y, Furuuchi K, Kojima Y, Tykocinski ML, Greene MI, Tone M (2008) Smad3 and NFAT cooperate to induce Foxp3 expression through its enhancer. Nat Immunol 9:194–202CrossRefPubMedGoogle Scholar
  54. Toulza F, Heaps A, Tanaka Y, Taylor GP, Bangham CR (2008) High frequency of CD4+FoxP3+ cells in HTLV-1 infection: inverse correlation with HTLV-1-specific CTL response. Blood 111:5047–53CrossRefPubMedPubMedCentralGoogle Scholar
  55. Uchiyama T (1997) Human T cell leukemia virus type I (HTLV-I) and human diseases. Annu Rev Immunol 15:15–37CrossRefPubMedGoogle Scholar
  56. Uchiyama T, Yodoi J, Sagawa K, Takatsuki K, Uchino H (1977) Adult T-cell leukemia: clinical and hematologic features of 16 cases. Blood 50:481–92PubMedGoogle Scholar
  57. Usui T, Yanagihara K, Tsukasaki K, Murata K, Hasegawa H, Yamada Y, Kamihira S (2008) Characteristic expression of HTLV-1 basic zipper factor (HBZ) transcripts in HTLV-1 provirus-positive cells. Retrovirology 5:34CrossRefPubMedPubMedCentralGoogle Scholar
  58. van Tienen C, de Silva TI, Alcantara LC, Onyango CO, Jarju S, Goncalves N, Vincent T, Aaby P, Whittle H, Schim van der Loeff M, Cotten M (2012) Molecular epidemiology of endemic human T-lymphotropic virus type 1 in a rural community in Guinea-Bissau. PLoS Negl Trop Dis 6:e1690CrossRefPubMedPubMedCentralGoogle Scholar
  59. Verdonck K, Gonzalez E, Van Dooren S, Vandamme AM, Vanham G, Gotuzzo E (2007) Human T-lymphotropic virus 1: recent knowledge about an ancient infection. Lancet Infect Dis 7:266–81CrossRefPubMedGoogle Scholar
  60. Walker MR, Kasprowicz DJ, Gersuk VH, Benard A, Van Landeghen M, Buckner JH, Ziegler SF (2003) Induction of FoxP3 and acquisition of T regulatory activity by stimulated human CD4+CD25− T cells. J Clin Invest 112:1437–43CrossRefPubMedGoogle Scholar
  61. Wolfe ND, Heneine W, Carr JK, Garcia AD, Shanmugam V, Tamoufe U, Torimiro JN, Prosser AT, Lebreton M, Mpoudi-Ngole E, McCutchan FE, Birx DL, Folks TM, Burke DS, Switzer WM (2005) Emergence of unique primate T-lymphotropic viruses among central African bushmeat hunters. Proc Natl Acad Sci U S A 102:7994–9CrossRefPubMedPubMedCentralGoogle Scholar
  62. Xu C, Zhou W, Wang Y, Qiao L (2014) Hepatitis B virus-induced hepatocellular carcinoma. Cancer Lett 345:216–22CrossRefPubMedGoogle Scholar
  63. Yamamoto-Taguchi N, Satou Y, Miyazato P, Ohshima K, Nakagawa M, Katagiri K, Kinashi T, Matsuoka M (2013) HTLV-1 bZIP factor induces inflammation through labile Foxp3 expression. PLoS Pathog 9:e1003630CrossRefPubMedPubMedCentralGoogle Scholar
  64. Yamano Y, Takenouchi N, Li HC, Tomaru U, Yao K, Grant CW, Maric DA, Jacobson S (2005) Virus-induced dysfunction of CD4+CD25+ T cells in patients with HTLV-I-associated neuroimmunological disease. J Clin Invest 115:1361–8CrossRefPubMedPubMedCentralGoogle Scholar
  65. Yang C, Li M, Newman RD, Shi YP, Ayisi J, van Eijk AM, Otieno J, Misore AO, Steketee RW, Nahlen BL, Lal RB (2003) Genetic diversity of HIV-1 in western Kenya: subtype-specific differences in mother-to-child transmission. AIDS 17:1667–74CrossRefPubMedGoogle Scholar
  66. Yoshida M, Satou Y, Yasunaga J, Fujisawa J, Matsuoka M (2008) Transcriptional control of spliced and unspliced human T-cell leukemia virus type 1 bZIP factor (HBZ) gene. J Virol 82:9359–68CrossRefPubMedPubMedCentralGoogle Scholar
  67. Zhang J, Yamada O, Matsushita Y, Chagan-Yasutan H, Hattori T (2010) Transactivation of human osteopontin promoter by human T-cell leukemia virus type 1-encoded Tax protein. Leuk Res 34:763–8CrossRefPubMedGoogle Scholar
  68. Zhao T, Satou Y, Sugata K, Miyazato P, Green PL, Imamura T, Matsuoka M (2011) HTLV-1 bZIP factor enhances TGF-beta signaling through p300 coactivator. Blood 118:1865–76CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Journal of NeuroVirology, Inc. 2015

Authors and Affiliations

  • Keiko Yasuma
    • 1
  • Toshio Matsuzaki
    • 2
  • Yoshihisa Yamano
    • 3
  • Hiroshi Takashima
    • 2
  • Masao Matsuoka
    • 1
  • Mineki Saito
    • 4
  1. 1.Laboratory of Virus Control, Institute for Virus ResearchKyoto UniversityKyotoJapan
  2. 2.Department of Neurology and GeriatricsKagoshima University Graduate School of Medical and Dental SciencesKagoshimaJapan
  3. 3.Department of Rare Diseases Research, Institute of Medical ScienceSt. Marianna University School of MedicineKanagawaJapan
  4. 4.Department of MicrobiologyKawasaki Medical SchoolKurashikiJapan

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