[en] Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus that causes
cancer (Adult T cell Leukemia, ATL) and a spectrum of inflammatory diseases (mainly
HTLV-associated myelopathy—tropical spastic paraparesis, HAM/TSP). Since virions are
particularly unstable, HTLV-1 transmission primarily occurs by transfer of a cell carrying
an integrated provirus. After transcription, the viral genomic RNA undergoes reverse
transcription and integration into the chromosomal DNA of a cell from the newly infected
host. The virus then replicates by either one of two modes: (i) an infectious cycle by virus
budding and infection of new targets and (ii) mitotic division of cells harboring an integrated
provirus. HTLV-1 replication initiates a series of mechanisms in the host including antiviral
immunity and checkpoint control of cell proliferation. HTLV-1 has elaborated strategies to
counteract these defense mechanisms allowing continuous persistence in humans.
Disciplines :
Oncology
Author, co-author :
Carpentier, Alexandre ; Université de Liège > Agronomie, Bio-ingénierie et Chimie (AgroBioChem) > Biologie cell. et moléc.
Gessain, A.; Cassar, O. Epidemiological Aspects and World Distribution of HTLV-1 Infection. Front. Microbiol. 2012, 3, e388.
Verdonck, K.; Gonzalez, E.; Van Dooren, S.; Vandamme, A.M.; Vanham, G.; Gotuzzo, E. Human T-lymphotropic virus 1: Recent knowledge about an ancient infection. Lancet. Infect. Dis. 2007, 7, 266–281.
Bazarbachi, A.; Plumelle, Y.; Carlos Ramos, J.; Tortevoye, P.; Otrock, Z.; Taylor, G.; Gessain, A.; Harrington, W.; Panelatti, G.; Hermine, O. 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. 2010, 28, 4177–4183.
Shiratori, S.; Yasumoto, A.; Tanaka, J.; Shigematsu, A.; Yamamoto, S.; Nishio, M.; Hashino, S.; Morita, R.; Takahata, M.; Onozawa, M.; et al. A retrospective analysis of allogeneic hematopoietic stem cell transplantation for adult T cell leukemia/lymphoma (ATL): Clinical impact of graft-versus-leukemia/lymphoma effect. Biol. Blood Marrow Transpl. 2008, 14, 817–823.
Ishida, T.; Hishizawa, M.; Kato, K.; Tanosaki, R.; Fukuda, T.; Takatsuka, Y.; Eto, T.; Miyazaki, Y.; Hidaka, M.; Uike, N.; et al. Impact of graft-versus-host disease on allogeneic hematopoietic cell transplantation for adult T cell leukemia-lymphoma focusing on preconditioning regimens: Nationwide retrospective study. Biol. Blood Marrow Transpl. 2013, 19, 1731–1739.
Ishida, T.; Hishizawa, M.; Kato, K.; Tanosaki, R.; Fukuda, T.; Taniguchi, S.; Eto, T.; Takatsuka, Y.; Miyazaki, Y.; Moriuchi, Y.; et al. Allogeneic hematopoietic stem cell transplantation for adult T-cell leukemia-lymphoma with special emphasis on preconditioning regimen: A nationwide retrospective study. Blood 2012, 120, 1734–1741.
Utsunomiya, A.; Choi, I.; Chihara, D.; Seto, M. Recent advances in the treatment of adult T-cell leukemia-lymphomas. Cancer Sci. 2015, 106, 344–351.
Yamauchi, J.; Coler-Reilly, A.; Sato, T.; Araya, N.; Yagishita, N.; Ando, H.; Kunitomo, Y.; Takahashi, K.; Tanaka, Y.; Shibagaki, Y.; et al. Mogamulizumab, an anti-CCR4 antibody, targets human T-lymphotropic virus type 1-infected CD8+ and CD4+ T cells to treat associated myelopathy. J. Infect. Dis. 2015, 211, 238–248.
Katz, R.A.; Skalka, A.M. Generation of Diversity in Retroviruses. Annu. Rev. Genet. 1990, 24, 409–443.
Matsuoka, M.; Jeang, K.T. Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nat. Rev. Cancer 2007, 7, 270–280.
Macatonia, S.E.; Cruickshank, J.K.; Rudge, P.; Knight, S.C. Dendritic cells from patients with tropical spastic paraparesis are infected with HTLV-1 and stimulate autologous lymphocyte proliferation. AIDS Res. Hum. Retrovir. 1992, 8, 1699–1706.
Koyanagi, Y.; Itoyama, Y.; Nakamura, N.; Takamatsu, K.; Kira, J.; Iwamasa, T.; Goto, I.; Yamamoto, N. In vivo infection of human T-cell leukemia virus type I in non-T cells. Virology 1993, 196, 25–33.
Jones, K.S.; Petrow-Sadowski, C.; Huang, Y.K.; Bertolette, D.C.; Ruscetti, F.W. Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4+ T cells. Nat. Med. 2008, 14, 429–436.
Manel, N.; Kim, F.J.; Kinet, S.; Taylor, N.; Sitbon, M.; Battini, J.L. The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV. Cell 2003, 115, 449–459.
Jones, K.S.; Petrow-Sadowski, C.; Bertolette, D.C.; Huang, Y.; Ruscetti, F.W. Heparan sulfate proteoglycans mediate attachment and entry of human T-cell leukemia virus type 1 virions into CD4+ T cells. J. Virol. 2005, 79, 12692–12702.
Ghez, D.; Lepelletier, Y.; Lambert, S.; Fourneau, J.M.; Blot, V.; Janvier, S.; Arnulf, B.; van Endert, P.M.; Heveker, N.; Pique, C.; et al. Neuropilin-1 is involved in human T-cell lymphotropic virus type 1 entry. J. Virol. 2006, 80, 6844–6854.
Lambert, S.; Bouttier, M.; Vassy, R.; Seigneuret, M.; Petrow-Sadowski, C.; Janvier, S.; Heveker, N.; Ruscetti, F.W.; Perret, G.; Jones, K.S.; et al. HTLV-1 uses HSPG and neuropilin-1 for entry by molecular mimicry of VEGF165. Blood 2009, 113, 5176–5185.
Ghez, D.; Lepelletier, Y.; Jones, K.S.; Pique, C.; Hermine, O. Current concepts regarding the HTLV-1 receptor complex. Retrovirology 2010, 7, e99.
Jones, K.S.; Lambert, S.; Bouttier, M.; Benit, L.; Ruscetti, F.W.; Hermine, O.; Pique, C. Molecular aspects of HTLV-1 entry: Functional domains of the HTLV-1 surface subunit (SU) and their relationships to the entry receptors. Viruses 2011, 3, 794–810.
21. Hoshino, H. Cellular Factors Involved in HTLV-1 Entry and Pathogenicit. Front. Microbiol. 2012, 3, e222.
Derse, D.; Hill, S.A.; Lloyd, P.A.; Chung, H.; Morse, B.A. J. Virol. 2001, 75, 8461–8468. Examining human T-lymphotropic virus type 1 infection and replication by cell-free infection with recombinant virus vectors.
Mazurov, D.; Ilinskaya, A.; Heidecker, G.; Lloyd, P.; Derse, D. Quantitative comparison of HTLV-1 and HIV-1 cell-to-cell infection with new replication dependent vectors. PLoS Pathog. 2010, 6, e1000788.
Goncalves, D.U.; Proietti, F.A.; Ribas, J.G.; Araujo, M.G.; Pinheiro, S.R.; Guedes, A.C.; Carneiro-Proietti, A.B. Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases. Clin. Microbiol. Rev. 2010, 23, 577–589.
Takeuchi, H.; Takahashi, M.; Norose, Y.; Takeshita, T.; Fukunaga, Y.; Takahashi, H. Transformation of breast milk macrophages by HTLV-I: Implications for HTLV-I transmission via breastfeeding. Biomed. Res. 2010, 31, 53–61.
Tugizov, S.M.; Herrera, R.; Veluppillai, P.; Greenspan, D.; Soros, V.; Greene, W.C.; Levy, J.A.; Palefsky, J.M. Differential transmission of HIV traversing fetal oral/intestinal epithelia and adult oral epithelia. J. Virol. 2012, 86, 2556–2570.
Martin-Latil, S.; Gnadig, N.F.; Mallet, A.; Desdouits, M.; Guivel-Benhassine, F.; Jeannin, P.; Prevost, M.C.; Schwartz, O.; Gessain, A.; Ozden, S.; et al. Transcytosis of HTLV-1 across a tight human epithelial barrier and infection of subepithelial dendritic cells. Blood 2012, 120, 572–580.
Pique, C.; Jones, K.S. Pathways of cell-cell transmission of HTLV-1. Front. Microbiol. 2012, 3, e378.
Igakura, T.; Stinchcombe, J.C.; Goon, P.K.; Taylor, G.P.; Weber, J.N.; Griffiths, G.M.; Tanaka, Y.; Osame, M.; Bangham, C.R. Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. Science 2003, 299, 1713–1716.
Majorovits, E.; Nejmeddine, M.; Tanaka, Y.; Taylor, G.P.; Fuller, S.D.; Bangham, C.R. Human T-lymphotropic virus-1 visualized at the virological synapse by electron tomography. PLoS ONE 2008, 3, e2251.
Nejmeddine, M.; Negi, V.S.; Mukherjee, S.; Tanaka, Y.; Orth, K.; Taylor, G.P.; Bangham, C.R. HTLV-1-Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse. Blood 2009, 114, 1016–1025.
Van Prooyen, N.; Gold, H.; Andresen, V.; Schwartz, O.; Jones, K.; Ruscetti, F.; Lockett, S.; Gudla, P.; Venzon, D.; Franchini, G. Human T-cell leukemia virus type 1 p8 protein increases cellular conduits and virus transmission. Proc. Natl. Acad. Sci. USA 2010, 107, 20738–20743.
Sze, A.; Belgnaoui, S.M.; Olagnier, D.; Lin, R.; Hiscott, J.; van Grevenynghe, J. Host restriction factor SAMHD1 limits human T cell leukemia virus type 1 infection of monocytes via STING-mediated apoptosis. Cell Host Microbe 2013, 14, 422–434.
Ooms, M.; Krikoni, A.; Kress, A.K.; Simon, V.; Munk, C. APOBEC3A, APOBEC3B, and APOBEC3H haplotype 2 restrict human T-lymphotropic virus type 1. J. Virol. 2012, 86, 6097–6108.
Bai, X.T.; Nicot, C. miR-28-3p is a cellular restriction factor that inhibits human T cell leukemia virus, type 1 (HTLV-1) replication and virus infection. J. Biol. Chem. 2015, 290, 5381–5390.
Twizere, J.C.; Kruys, V.; Lefebvre, L.; Vanderplasschen, A.; Collete, D.; Debacq, C.; Lai, W.S.; Jauniaux, J.C.; Bernstein, L.R.; Semmes, O.J.; et al. Interaction of retroviral Tax oncoproteins with tristetraprolin and regulation of tumor necrosis factor-alpha expression. J. Natl. Cancer Inst. 2003, 95, 1846–1859.
Boxus, M.; Twizere, J.C.; Legros, S.; Kettmann, R.; Willems, L. Interaction of HTLV-1 Tax with minichromosome maintenance proteins accelerates the replication timing program. Blood 2012, 119, 151–160.
Miyazato, P.; Yasunaga, J.; Taniguchi, Y.; Koyanagi, Y.; Mitsuya, H.; Matsuoka, M. De novo human T-cell leukemia virus type 1 infection of human lymphocytes in NOD-SCID, common gamma-chain knockout mice. J. Virol. 2006, 80, 10683–10691.
Taylor, G.P.; Goon, P.; Furukawa, Y.; Green, H.; Barfield, A.; Mosley, A.; Nose, H.; Babiker, A.; Rudge, P.; Usuku, K.; et al. Zidovudine plus lamivudine in Human T-Lymphotropic Virus type-I-associated myelopathy: A randomised trial. Retrovirology 2006, 3, e63.
Trevino, A.; Parra, P.; Bar-Magen, T.; Garrido, C.; de Mendoza, C.; Soriano, V. Antiviral effect of raltegravir on HTLV-1 carriers. J. Antimicrobial Chemother. 2012, 67, 218–221.
Asquith, B.; Zhang, Y.; Mosley, A.J.; de Lara, C.M.; Wallace, D.L.; Worth, A.; Kaftantzi, L.; Meekings, K.; Griffin, G.E.; Tanaka, Y.; et al. In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection. Proc. Natl. Acad. Sci. USA 2007, 104, 8035–8040.
Debacq, C.; Asquith, B.; Kerkhofs, P.; Portetelle, D.; Burny, A.; Kettmann, R.; Willems, L. Increased cell proliferation, but not reduced cell death, induces lymphocytosis in bovine leukemia virus-infected sheep. Proc. Natl. Acad. Sci. USA 2002, 99, 10048–10053.
Ratner, L.; Philpott, T.; Trowbridge, D.B. Nucleotide sequence analysis of isolates of human T-lymphotropic virus type 1 of diverse geographical origins. AIDS Res. Hum. Retrovir. 1991, 7, 923–941.
Gillet, N.A.; Malani, N.; Melamed, A.; Gormley, N.; Carter, R.; Bentley, D.; Berry, C.; Bushman, F.D.; Taylor, G.P.; Bangham, C.R. The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones. Blood 2011, 117, 3113–3122.
Gillet, N.A.; Gutierrez, G.; Rodriguez, S.M.; de Brogniez, A.; Renotte, N.; Alvarez, I.; Trono, K.; Willems, L. Massive depletion of bovine leukemia virus proviral clones located in genomic transcriptionally active sites during primary infection. PLoS Pathog. 2013, 9, e1003687.
Reid, R.L.; Lindholm, P.F.; Mireskandari, A.; Dittmer, J.; Brady, J.N. Stabilization of wild-type p53 in human T-lymphocytes transformed by HTLV-I. Oncogene 1993, 8, 3029–3036.
Takachi, T.; Takahashi, M.; Takahashi-Yoshita, M.; Higuchi, M.; Obata, M.; Mishima, Y.; Okuda, S.; Tanaka, Y.; Matsuoka, M.; Saitoh, A.; et al. Human T-cell leukemia virus type 1 Tax oncoprotein represses the expression of the BCL11B tumor suppressor in T-cells. Cancer Sci. 2015, 106, 461–465.
Yeung, M.L.; Yasunaga, J.; Bennasser, Y.; Dusetti, N.; Harris, D.; Ahmad, N.; Matsuoka, M.; Jeang, K.T. Roles for microRNAs, miR-93 and miR-130b, and tumor protein 53-induced nuclear protein 1 tumor suppressor in cell growth dysregulation by human T-cell lymphotrophic virus 1. Cancer Res. 2008, 68, 8976–8985.
51. Boxus, M.; Twizere, J.C.; Legros, S.; Dewulf, J.F.; Kettmann, R.; Willems, L. The HTLV-1 Tax interactome. Retrovirology 2008, 5, e76.
Jin, D.Y.; Spencer, F.; Jeang, K.T. Human T cell leukemia virus type 1 oncoprotein Tax targets the human mitotic checkpoint protein MAD1. Cell 1998, 93, 81–91.
Kinjo, T.; Ham-Terhune, J.; Peloponese, J.M., Jr.; Jeang, K.T. 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. 2010, 84, 5431–5437.
Grossman, W.J.; Kimata, J.T.; Wong, F.H.; Zutter, M.; Ley, T.J.; Ratner, L. Development of leukemia in mice transgenic for the tax gene of human T-cell leukemia virus type I. Proc. Natl. Acad. Sci. USA 1995, 92, 1057–1061.
Hasegawa, H.; Sawa, H.; Lewis, M.J.; Orba, Y.; Sheehy, N.; Yamamoto, Y.; Ichinohe, T.; Tsunetsugu-Yokota, Y.; Katano, H.; Takahashi, H.; et al. Thymus-derived leukemia-lymphoma in mice transgenic for the Tax gene of human T-lymphotropic virus type I. Nat. Med. 2006, 12, 466–472.
Ohsugi, T.; Kumasaka, T.; Okada, S.; Urano, T. The Tax protein of HTLV-1 promotes oncogenesis in not only immature T cells but also mature T cells. Nat. Med. 2007, 13, 527–528.
Chaib-Mezrag, H.; Lemacon, D.; Fontaine, H.; Bellon, M.; Bai, X.T.; Drac, M.; Coquelle, A.; Nicot, C. Tax impairs DNA replication forks and increases DNA breaks in specific oncogenic genome regions. Mol. Cancer 2014, 13, 205.
Marriott, S.J.; Semmes, O.J. Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response. Oncogene 2005, 24, 5986–5995.
Bellon, M.; Baydoun, H.H.; Yao, Y.; Nicot, C. HTLV-I Tax-dependent and -independent events associated with immortalization of human primary T lymphocytes. Blood 2010, 115, 2441–2448.
Nakagawa, M.; Schmitz, R.; Xiao, W.; Goldman, C.K.; Xu, W.; Yang, Y.; Yu, X.; Waldmann, T.A.; Staudt, L.M. Gain-of-function CCR4 mutations in adult T cell leukemia/lymphoma. J. Exp. Med. 2014, 211, 2497–2505.
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.
Koiwa, T.; Hamano-Usami, A.; Ishida, T.; Okayama, A.; Yamaguchi, K.; Kamihira, S.; Watanabe, T. 51 -long terminal repeat-selective CpG methylation of latent human T-cell leukemia virus type 1 provirus in vitro and in vivo. J. Virol. 2002, 76, 9389–9397.
Takeda, S.; Maeda, M.; Morikawa, S.; Taniguchi, Y.; Yasunaga, J.; Nosaka, K.; Tanaka, Y.; Matsuoka, M. Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells. Int. J. Cancer 2004, 109, 559–567.
65. Taniguchi, Y.; Nosaka, K.; Yasunaga, J.; Maeda, M.; Mueller, N.; Okayama, A.; Matsuoka, M. Silencing of human T-cell leukemia virus type I gene transcription by epigenetic mechanisms. Retrovirology 2005, 2, e64.
Jacobson, S.; Shida, H.; McFarlin, D.E.; Fauci, A.S.; 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.
Kannagi, M.; Harada, S.; Maruyama, I.; Inoko, H.; Igarashi, H.; Kuwashima, G.; Sato, S.; Morita, M.; Kidokoro, M.; Sugimoto, M.; et al. 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. 1991, 3, 761–767.
Kannagi, M.; Matsushita, S.; Harada, S. Expression of the target antigen for cytotoxic T lymphocytes on adult T-cell-leukemia cells. Int. J. Cancer 1993, 54, 582–588.
Satou, Y.; Yasunaga, J.; Yoshida, M.; Matsuoka, M. HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells. Proc. Natl. Acad. Sci. USA 2006, 103, 720–725.
Macnamara, A.; Rowan, A.; Hilburn, S.; Kadolsky, U.; Fujiwara, H.; Suemori, K.; Yasukawa, M.; Taylor, G.; Bangham, C.R.; Asquith, B. HLA class I binding of HBZ determines outcome in HTLV-1 infection. PLoS Pathog. 2010, 6, e1001117.
Hilburn, S.; Rowan, A.; Demontis, M.A.; MacNamara, A.; Asquith, B.; Bangham, C.R.; Taylor, G.P. 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. 2011, 203, 529–536.
Matsuoka, M.; Jeang, K.T. Human T-cell leukemia virus type 1 (HTLV-1) and leukemic transformation: Viral infectivity, Tax, HBZ and therapy. Oncogene 2011, 30, 1379–1389.
Andrade, R.G.; Goncalves Pde, C.; Ribeiro, M.A.; Romanelli, L.C.; Ribas, J.G.; Torres, E.B.; Carneiro-Proietti, A.B.; Barbosa-Stancioli, E.F.; Martins, M.L. Strong correlation between tax and HBZ mRNA expression in HAM/TSP patients: Distinct markers for the neurologic disease. J. Clin. Virol. 2013, 56, 135–140.
Saito, M.; Matsuzaki, T.; Satou, Y.; Yasunaga, J.; Saito, K.; Arimura, K.; Matsuoka, M.; Ohara, Y. 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 2009, 6, e19.
Sun, S.C.; Yamaoka, S. Activation of NF-kappaB by HTLV-I and implications for cell transformation. Oncogene 2005, 24, 5952–5964.
Pujari, R.; Hunte, R.; Thomas, R.; van der Weyden, L.; Rauch, D.; Ratner, L.; Nyborg, J.K.; Ramos, J.C.; Takai, Y.; Shembade, N. Human T-cell leukemia virus type 1 (HTLV-1) tax requires CADM1/TSLC1 for inactivation of the NF-kappaB inhibitor A20 and constitutive NF-kappaB signaling. PLoS Pathog. 2015, 11, e1004721.
Harhaj, E.W.; Harhaj, N.S. Mechanisms of persistent NF-kappaB activation by HTLV-I tax. IUBMB Life 2005, 57, 83–91.
Lavorgna, A.; Matsuoka, M.; Harhaj, E.W. A critical role for IL-17RB signaling in HTLV-1 tax-induced NF-kappaB activation and T-cell transformation. PLoS Pathog. 2014, 10, e1004418.
Lavorgna, A.; Harhaj, E.W. Regulation of HTLV-1 tax stability, cellular trafficking and NF-kappaB activation by the ubiquitin-proteasome pathway. Viruses 2014, 6, 3925-3943.
Karin, M. NF-kappaB as a critical link between inflammation and cancer. Cold Spring Harb. Perspect. Biol. 2009, 1.
Xiao, G.; Fu, J. NF-kappaB and cancer: A paradigm of Yin-Yang. Am. J. Cancer Res. 2011, 1, 192–221.
Krueger, A.; Fas, S.C.; Giaisi, M.; Bleumink, M.; Merling, A.; Stumpf, C.; Baumann, S.; Holtkotte, D.; Bosch, V.; Krammer, P.H.; et al. HTLV-1 Tax protects against CD95-mediated apoptosis by induction of the cellular FLICE-inhibitory protein (c-FLIP). Blood 2006, 107, 3933–3939.
Okamoto, K.; Fujisawa, J.; Reth, M.; Yonehara, S. Human T-cell leukemia virus type-I oncoprotein Tax inhibits Fas-mediated apoptosis by inducing cellular FLIP through activation of NF-kappaB. Genes Cells: Devoted Mol. Cell. Mech. 2006, 11, 177–191.
Tsukahara, T.; Kannagi, M.; Ohashi, T.; Kato, H.; Arai, M.; Nunez, G.; Iwanaga, Y.; Yamamoto, N.; Ohtani, K.; Nakamura, M.; et al. Induction of Bcl-x(L) expression by human T-cell leukemia virus type 1 Tax through NF-kappaB in apoptosis-resistant T-cell transfectants with Tax. J. Virol. 1999, 73, 7981–7987.
Nicot, C.; Mahieux, R.; Takemoto, S.; Franchini, G. Bcl-X(L) is up-regulated by HTLV-I and HTLV-II in vitro and in ex vivo ATLL samples. Blood 2000, 96, 275–281.
Macaire, H.; Riquet, A.; Moncollin, V.; Biemont-Trescol, M.C.; Duc Dodon, M.; Hermine, O.; Debaud, A.L.; Mahieux, R.; Mesnard, J.M.; Pierre, M.; et al. Tax protein-induced expression of antiapoptotic Bfl-1 protein contributes to survival of human T-cell leukemia virus type 1 (HTLV-1)-infected T-cells. J. Biol. Chem. 2012, 287, 21357–21370.
Zhao, T.; Yasunaga, J.; Satou, Y.; Nakao, M.; Takahashi, M.; Fujii, M.; Matsuoka, M. Human T-cell leukemia virus type 1 bZIP factor selectively suppresses the classical pathway of NF-kappaB. Blood 2009, 113, 2755–2764.
Zhi, H.; Yang, L.; Kuo, Y.L.; Ho, Y.K.; Shih, H.M.; Giam, C.Z. NF-kappaB hyper-activation by HTLV-1 tax induces cellular senescence, but can be alleviated by the viral anti-sense protein HBZ. PLoS Pathog. 2011, 7, e1002025.
Ho, Y.K.; Zhi, H.; DeBiaso, D.; Philip, S.; Shih, H.M.; Giam, C.Z. HTLV-1 tax-induced rapid senescence is driven by the transcriptional activity of NF-kappaB and depends on chronically activated IKKalpha and p65/RelA. J. Virol. 2012, 86, 9474–9483.
Philip, S.; Zahoor, M.A.; Zhi, H.; Ho, Y.K.; Giam, C.Z. Regulation of human T-lymphotropic virus type I latency and reactivation by HBZ and Rex. PLoS Pathog. 2014, 10, e1004040.
Peloponese, J.M., Jr.; Jeang, K.T. Role for Akt/protein kinase B and activator protein-1 in cellular proliferation induced by the human T-cell leukemia virus type 1 tax oncoprotein. J. Biol. Chem. 2006, 281, 8927–8938.
Tomita, M.; Semenza, G.L.; Michiels, C.; Matsuda, T.; Uchihara, J.N.; Okudaira, T.; Tanaka, Y.; Taira, N.; Ohshiro, K.; Mori, N. Activation of hypoxia-inducible factor 1 in human T-cell leukaemia virus type 1-infected cell lines and primary adult T-cell leukaemia cells. Biochem. J. 2007, 406, 317–323.
Higuchi, M.; Takahashi, M.; Tanaka, Y.; Fujii, M. Downregulation of proapoptotic Bim augments IL-2-independent T-cell transformation by human T-cell leukemia virus type-1 Tax. Cancer Med. 2014, 3, 1605–1614.
Saito, K.; Saito, M.; Taniura, N.; Okuwa, T.; Ohara, Y. Activation of the PI3K-Akt pathway by human T cell leukemia virus type 1 (HTLV-1) oncoprotein Tax increases Bcl3 expression, which is associated with enhanced growth of HTLV-1-infected T cells. Virology 2010, 403, 173–180.
Sugata, K.; Satou, Y.; Yasunaga, J.; Hara, H.; Ohshima, K.; Utsunomiya, A.; Mitsuyama, M.; Matsuoka, M. HTLV-1 bZIP factor impairs cell-mediated immunity by suppressing production of Th1 cytokines. Blood 2012, 119, 434–444.
Tanaka-Nakanishi, A.; Yasunaga, J.; Takai, K.; Matsuoka, M. HTLV-1 bZIP factor suppresses apoptosis by attenuating the function of FoxO3a and altering its localization. Cancer Res. 2014, 74, 188–200.
Matsumoto, J.; Ohshima, T.; Isono, O.; Shimotohno, K. HTLV-1 HBZ suppresses AP-1 activity by impairing both the DNA-binding ability and the stability of c-Jun protein. Oncogene 2005, 24, 1001–1010.
Hivin, P.; Basbous, J.; Raymond, F.; Henaff, D.; Arpin-Andre, C.; Robert-Hebmann, V.; Barbeau, B.; Mesnard, J.M. The HBZ-SP1 isoform of human T-cell leukemia virus type I represses JunB activity by sequestration into nuclear bodies. Retrovirology 2007, 4, e14.
Isono, O.; Ohshima, T.; Saeki, Y.; Matsumoto, J.; Hijikata, M.; Tanaka, K.; Shimotohno, K. Human T-cell leukemia virus type 1 HBZ protein bypasses the targeting function of ubiquitination. J. Biol. Chem. 2008, 283, 34273–34282.
Clerc, I.; Hivin, P.; Rubbo, P.A.; Lemasson, I.; Barbeau, B.; Mesnard, J.M. Propensity for HBZ-SP1 isoform of HTLV-I to inhibit c-Jun activity correlates with sequestration of c-Jun into nuclear bodies rather than inhibition of its DNA-binding activity. Virology 2009, 391, 195–202.
Ohshima, T.; Mukai, R.; Nakahara, N.; Matsumoto, J.; Isono, O.; Kobayashi, Y.; Takahashi, S.; Shimotohno, K. HTLV-1 basic leucine-zipper factor, HBZ, interacts with MafB and suppresses transcription through a Maf recognition element. J. Cell. Biochem. 2010, 111, 187–194.
Kashanchi, F.; Brady, J.N. Transcriptional and post-transcriptional gene regulation of HTLV-1. Oncogene 2005, 24, 5938–5951.
Saggioro, D.; Barp, S.; Chieco-Bianchi, L. Block of a mitochondrial-mediated apoptotic pathway in Tax-expressing murine fibroblasts. Exp. Cell Res. 2001, 269, 245–255.
Trevisan, R.; Daprai, L.; Acquasaliente, L.; Ciminale, V.; Chieco-Bianchi, L.; Saggioro, D. Relevance of CREB phosphorylation in the anti-apoptotic function of human T-lymphotropic virus type 1 tax protein in serum-deprived murine fibroblasts. Exp. Cell Res. 2004, 299, 57–67.
Trevisan, R.; Daprai, L.; Paloschi, L.; Vajente, N.; Chieco-Bianchi, L.; Saggioro, D. Antiapoptotic effect of human T-cell leukemia virus type 1 tax protein correlates with its creb transcriptional activity. Exp. Cell Res. 2006, 312, 1390–1400.
Saggioro, D. Anti-apoptotic effect of Tax: An NF-kappaB path or a CREB way? Viruses 2011, 3, 1001–1014.
Saggioro, D.; Silic-Benussi, M.; Biasiotto, R.; D’Agostino, D.M.; Ciminale, V. Control of cell death pathways by HTLV-1 proteins. Front. Biosci. 2009, 14, 3338–3351.
Fukuda, R.I.; Tsuchiya, K.; Suzuki, K.; Itoh, K.; Fujita, J.; Utsunomiya, A.; Tsuji, T. Human T-cell leukemia virus type I tax down-regulates the expression of phosphatidylinositol 3,4,5-trisphosphate inositol phosphatases via the NF-kappaB pathway. J. Biol. Chem. 2009, 284, 2680–2689.
Gaudray, G.; Gachon, F.; Basbous, J.; Biard-Piechaczyk, M.; Devaux, C.; Mesnard, J.M. 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.
Lemasson, I.; Lewis, M.R.; Polakowski, N.; Hivin, P.; Cavanagh, M.H.; Thebault, S.; Barbeau, B.; Nyborg, J.K.; Mesnard, J.M. 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. 2007, 81, 1543–1553.
Clerc, I.; Polakowski, N.; Andre-Arpin, C.; Cook, P.; Barbeau, B.; Mesnard, J.M.; Lemasson, I. An interaction between the human T cell leukemia virus type 1 basic leucine zipper factor (HBZ) and the KIX domain of p300/CBP contributes to the down-regulation of tax-dependent viral transcription by HBZ. J. Biol. Chem. 2008, 283, 23903–23913.
Cook, P.R.; Polakowski, N.; Lemasson, I. HTLV-1 HBZ protein deregulates interactions between cellular factors and the KIX domain of p300/CBP. J. Mol. Biol. 2011, 409, 384–398.
Ma, G.; Yasunaga, J.; Fan, J.; Yanagawa, S.; Matsuoka, M. HTLV-1 bZIP factor dysregulates the Wnt pathways to support proliferation and migration of adult T-cell leukemia cells. Oncogene 2013, 32, 4222–4230.
Arnulf, B.; Villemain, A.; Nicot, C.; Mordelet, E.; Charneau, P.; Kersual, J.; Zermati, Y.; Mauviel, A.; Bazarbachi, A.; Hermine, O. 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.
Lee, D.K.; Kim, B.C.; Brady, J.N.; Jeang, K.T.; Kim, S.J. 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. 2002, 277, 33766–33775.
Mori, N.; Morishita, M.; Tsukazaki, T.; Giam, C.Z.; Kumatori, A.; Tanaka, Y.; Yamamoto, N. 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.
Kim, Y.M.; Geiger, T.R.; Egan, D.I.; Sharma, N.; Nyborg, J.K. The HTLV-1 tax protein cooperates with phosphorylated CREB, TORC2 and p300 to activate CRE-dependent cyclin D1 transcription. Oncogene 2010, 29, 2142–2152.
Dellino, G.I.; Cittaro, D.; Piccioni, R.; Luzi, L.; Banfi, S.; Segalla, S.; Cesaroni, M.; Mendoza-Maldonado, R.; Giacca, M.; Pelicci, P.G. Genome-wide mapping of human DNA-replication origins: Levels of transcription at ORC1 sites regulate origin selection and replication timing. Genome Res. 2013, 23, 1–11.
Ma, Y.; Zheng, S.; Wang, Y.; Zang, W.; Li, M.; Wang, N.; Li, P.; Jin, J.; Dong, Z.; Zhao, G. The HTLV-1 HBZ protein inhibits cyclin D1 expression through interacting with the cellular transcription factor CREB. Mol. Biol. Rep. 2013, 40, 5967–5975.
Hagiya, K.; Yasunaga, J.; Satou, Y.; Ohshima, K.; Matsuoka, M. ATF3, an HTLV-1 bZip factor binding protein, promotes proliferation of adult T-cell leukemia cells. Retrovirology 2011, 8, e19.
Tabakin-Fix, Y.; Azran, I.; Schavinky-Khrapunsky, Y.; Levy, O.; Aboud, M. Functional inactivation of p53 by human T-cell leukemia virus type 1 Tax protein: Mechanisms and clinical implications. Carcinogenesis 2006, 27, 673–681.
Ariumi, Y.; Kaida, A.; Lin, J.Y.; Hirota, M.; Masui, O.; Yamaoka, S.; Taya, Y.; Shimotohno, K. HTLV-1 tax oncoprotein represses the p53-mediated trans-activation function through coactivator CBP sequestration. Oncogene 2000, 19, 1491–1499.
Pise-Masison, C.A.; Mahieux, R.; Jiang, H.; Ashcroft, M.; Radonovich, M.; Duvall, J.; Guillerm, C.; Brady, J.N. 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.
Miyazato, A.; Sheleg, S.; Iha, H.; Li, Y.; Jeang, K.T. Evidence for NF-kappaB- and CBP-independent repression of p53’s transcriptional activity by human T-cell leukemia virus type 1 Tax in mouse embryo and primary human fibroblasts. J. Virol. 2005, 79, 9346–9350.
Liu, B.; Hong, S.; Tang, Z.; Yu, H.; Giam, C.Z. HTLV-I Tax directly binds the Cdc20-associated anaphase-promoting complex and activates it ahead of schedule. Proc. Natl. Acad. Sci. USA 2005, 102, 63–68.
Peloponese, J.M., Jr.; Haller, K.; Miyazato, A.; Jeang, K.T. Abnormal centrosome amplification in cells through the targeting of Ran-binding protein-1 by the human T cell leukemia virus type-1 Tax oncoprotein. Proc. Natl. Acad. Sci. USA 2005, 102, 18974–18979.
Haoudi, A.; Semmes, O.J. The HTLV-1 tax oncoprotein attenuates DNA damage induced G1 arrest and enhances apoptosis in p53 null cells. Virology 2003, 305, 229–239.
Park, H.U.; Jeong, J.H.; Chung, J.H.; Brady, J.N. Human T-cell leukemia virus type 1 Tax interacts with Chk1 and attenuates DNA-damage induced G2 arrest mediated by Chk1. Oncogene 2004, 23, 4966–4974.
Park, H.U.; Jeong, S.J.; Jeong, J.H.; Chung, J.H.; Brady, J.N. Human T-cell leukemia virus type 1 Tax attenuates gamma-irradiation-induced apoptosis through physical interaction with Chk2. Oncogene 2006, 25, 438–447.
Gupta, S.K.; Guo, X.; Durkin, S.S.; Fryrear, K.F.; Ward, M.D.; Semmes, O.J. Human T-cell leukemia virus type 1 Tax oncoprotein prevents DNA damage-induced chromatin egress of hyperphosphorylated Chk2. J. Biol. Chem. 2007, 282, 29431–29440.
Chandhasin, C.; Ducu, R.I.; Berkovich, E.; Kastan, M.B.; Marriott, S.J. Human T-cell leukemia virus type 1 tax attenuates the ATM-mediated cellular DNA damage response. J. Virol. 2008, 82, 6952–6961.
Durkin, S.S.; Guo, X.; Fryrear, K.A.; Mihaylova, V.T.; Gupta, S.K.; Belgnaoui, S.M.; Haoudi, A.; Kupfer, G.M.; Semmes, O.J. HTLV-1 Tax oncoprotein subverts the cellular DNA damage response via binding to DNA-dependent protein kinase. J. Biol. Chem. 2008, 283, 36311–36320.
Belgnaoui, S.M.; Fryrear, K.A.; Nyalwidhe, J.O.; Guo, X.; Semmes, O.J. The viral oncoprotein tax sequesters DNA damage response factors by tethering MDC1 to chromatin. J. Biol. Chem. 2010, 285, 32897–32905.
Boxus, M.; Willems, L. How the DNA damage response determines the fate of HTLV-1 Tax-expressing cells. Retrovirology 2012, 9, e2.
Vernin, C.; Thenoz, M.; Pinatel, C.; Gessain, A.; Gout, O.; Delfau-Larue, M.H.; Nazaret, N.; Legras-Lachuer, C.; Wattel, E.; Mortreux, F. HTLV-1 bZIP Factor HBZ Promotes Cell Proliferation and Genetic Instability by Activating OncomiRs. Cancer Res. 2014, 74, 6082–6093.
Mukai, R.; Ohshima, T. HTLV-1 HBZ positively regulates the mTOR signaling pathway via inhibition of GADD34 activity in the cytoplasm. Oncogene 2014, 33, 2317–2328.
Jeang, K.T.; Widen, S.G.; Semmes, O.J.t.; Wilson, S.H. HTLV-I trans-activator protein, tax, is a trans-repressor of the human beta-polymerase gene. Science 1990, 247, 1082–1084.
Philpott, S.M.; Buehring, G.C. Defective DNA repair in cells with human T-cell leukemia/bovine leukemia viruses: Role of tax gene. J. Natl. Cancer Inst. 1999, 91, 933–942.
Kao, S.Y.; Marriott, S.J. Disruption of nucleotide excision repair by the human T-cell leukemia virus type 1 Tax protein. J. Virol. 1999, 73, 4299–4304.
Lemoine, F.J.; Kao, S.Y.; Marriott, S.J. Suppression of DNA repair by HTLV type 1 Tax correlates with Tax trans-activation of proliferating cell nuclear antigen gene expression. AIDS Res. Hum. Retrovir. 2000, 16, 1623–1627.
Majone, F.; Jeang, K.T. Unstabilized DNA breaks in HTLV-1 Tax expressing cells correlate with functional targeting of Ku80, not PKcs, XRCC4, or H2AX. Cell Biosci. 2012, 2, e15.
Baydoun, H.H.; Bai, X.T.; Shelton, S.; Nicot, C. HTLV-I tax increases genetic instability by inducing DNA double strand breaks during DNA replication and switching repair to NHEJ. PLoS ONE 2012, 7, e42226.
Baydoun, H.H.; Pancewicz, J.; Nicot, C. Human T-lymphotropic type 1 virus p30 inhibits homologous recombination and favors unfaithful DNA repair. Blood 2011, 117, 5897–5906.
