1887

Abstract

Human T-lymphotropic virus type 1 (HTLV-1) varies little in sequence compared with human immunodeficiency virus type 1 (HIV) and it is difficult to detect HTLV-1 mRNA, proteins or virions in fresh blood. But the strong and chronically activated T cell response to the virus indicates that HTLV-1 proteins are expressed persistently. It now appears that the efficiency of an individual's cytotoxic T cell (CTL) response to HTLV-1 is the chief single determinant of that person's provirus load, which can differ between HTLV-1-infected people by more than 10 000-fold. Progress is now being made towards defining this CTL ‘efficiency’ in terms of host genetics, T cell function, T cell gene expression and mathematical dynamics. Lymphocytes that are naturally infected with HTLV-1 do not produce enveloped extracellular virions in short-term culture and this has reinforced the erroneous conclusion that the virus is latent. But recent evidence shows that HTLV-1 can spread directly between lymphocytes across a specialized, virus-induced cell–cell contact – a ‘viral synapse’. Instead of making extracellular virions, HTLV-1 uses the mobility of the host cell to spread within and between hosts. In this review the evidence is summarized on the persistent gene expression of HTLV-1 , the role of the immune system in protection and pathogenesis in HTLV-1 infection, and the mechanism of cell-to-cell spread of HTLV-1.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/vir.0.19334-0
2003-12-01
2019-10-23
Loading full text...

Full text loading...

/deliver/fulltext/jgv/84/12/vir843177.html?itemId=/content/journal/jgv/10.1099/vir.0.19334-0&mimeType=html&fmt=ahah

References

  1. Addo, M. M., Yu, X. G., Rathod, A. & 17 other authors ( 2003; ). Comprehensive epitope analysis of human immunodeficiency virus type 1 (HIV-1)-specific T-cell responses directed against the entire expressed HIV-1 genome demonstrate broadly directed responses, but no correlation to viral load. J Virol 77, 2081–2092.[CrossRef]
    [Google Scholar]
  2. Albrecht, B. & Lairmore, M. D. ( 2002; ). Critical role of human T-lymphotropic virus type 1 accessory proteins in viral replication and pathogenesis. Microbiol Mol Biol Rev 66, 396–406.[CrossRef]
    [Google Scholar]
  3. Asquith, B. & Bangham, C. R. ( 2000; ). The role of cytotoxic T lymphocytes in human T-cell lymphotropic virus type 1 infection. J Theor Biol 207, 65–79.[CrossRef]
    [Google Scholar]
  4. Bangham, C. R. ( 2000; ). The immune response to HTLV-I. Curr Opin Immunol 12, 397–402.[CrossRef]
    [Google Scholar]
  5. Bangham, C. R. M. ( 2002; ). Genetics and dynamics of the immune response to HTLV-I. Gann Monogr Cancer Res 50, 397–402.
    [Google Scholar]
  6. Bangham, C. R. M., Kermode, A. G., Hall, S. E. & Daenke, S. ( 1996; ). The cytotoxic T-lymphocyte response to HTLV-I: the main determinant of disease? Semin Virol 7, 41–48.[CrossRef]
    [Google Scholar]
  7. Betts, M. R., Ambrozak, D. R., Douek, D. C., Bonhoeffer, S., Brenchley, J. M., Casazza, J. P., Koup, R. A. & Picker, L. J. ( 2001; ). Analysis of total human immunodeficiency virus (HIV)-specific CD4+ and CD8+ T-cell responses: relationship to viral load in untreated HIV infection. J Virol 75, 11983–11991.[CrossRef]
    [Google Scholar]
  8. Buchmeier, M. J., Welsh, R. M., Dutko, F. J. & Oldstone, M. B. ( 1980; ). The virology and immunobiology of lymphocytic choriomeningitis virus infection. Adv Immunol 30, 275–331.
    [Google Scholar]
  9. Carrington, M., Nelson, G. W., Martin, M. P. & 7 other authors ( 1999; ). HLA and HIV-1: heterozygote advantage and B*35-Cw*04 disadvantage. Science 283, 1748–1752.[CrossRef]
    [Google Scholar]
  10. Daenke, S., Kermode, A. G., Hall, S. E., Taylor, G., Weber, J., Nightingale, S. & Bangham, C. R. ( 1996; ). High activated and memory cytotoxic T-cell responses to HTLV-1 in healthy carriers and patients with tropical spastic paraparesis. Virology 217, 139–146.[CrossRef]
    [Google Scholar]
  11. Fan, N., Gavalchin, J., Paul, B., Wells, K. H., Lane, M. J. & Poiesz, B. J. ( 1992; ). Infection of peripheral blood mononuclear cells and cell lines by cell-free human T-cell lymphoma/leukemia virus type I. J Clin Microbiol 30, 905–910.
    [Google Scholar]
  12. Ford, W. L. ( 1975; ). Lymphocyte migration and immune responses. Prog Allergy 19, 1–59.
    [Google Scholar]
  13. 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, 1343–1349.[CrossRef]
    [Google Scholar]
  14. Gasmi, M., D'Incan, M. & Desgranges, C. ( 1997; ). Transfusion transmission of human T-lymphotropic virus type I (HTLV-I) from an asymptomatic blood donor: conservation of LTR U3, env, and tax nucleotide sequences in a recipient with HTLV-I-associated myelopathy. Transfusion 37, 60–64.[CrossRef]
    [Google Scholar]
  15. Goon, P. K. C., Hanon, E., Igakura, T., Tanaka, Y., Weber, J. N., Taylor, G. P. & Bangham, C. R. M. ( 2002; ). High frequencies of Th1 type CD4+ T-cells specific to HTLV-I Env and Tax proteins in patients with HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Blood 99, 3335–3341.[CrossRef]
    [Google Scholar]
  16. Grakoui, A., Bromley, S. K., Sumen, C., Davis, M. M., Shaw, A. S., Allen, P. M. & Dustin, M. L. ( 1999; ). The immunological synapse: a molecular machine controlling T cell activation. Science 285, 221–227.[CrossRef]
    [Google Scholar]
  17. Green, P. L. & Chen, I. S. Y. ( 2001; ). Human T-cell leukemia virus types 1 and 2. In Fields Virology, 4th edn, pp. 1941–1969. Edited by D. M. Knipe & P. M. Howley. Philadelphia: Lippincott Williams & Wilkins.
  18. Greten, T. F., Slansky, J. E., Kubota, R., Soldan, S. S., Jaffee, E. M., Leist, T. P., Pardoll, D. M., Jacobson, S. & Schneck, J. P. ( 1998; ). Direct visualization of antigen-specific T cells: HTLV-1 Tax11–19-specific CD8+ T cells are activated in peripheral blood and accumulate in cerebrospinal fluid from HAM/TSP patients. Proc Natl Acad Sci U S A 95, 7568–7573.[CrossRef]
    [Google Scholar]
  19. Hanon, E., Stinchcombe, J. C., Saito, M., Asquith, B. E., Taylor, G. P., Tanaka, Y., Weber, J. N., Griffiths, G. M. & Bangham, C. R. ( 2000a; ). Fratricide among CD8+ T lymphocytes naturally infected with human T cell lymphotropic virus type I. Immunity 13, 657–664.[CrossRef]
    [Google Scholar]
  20. Hanon, E., Hall, S., Taylor, G. P. & 7 other authors ( 2000b; ). Abundant tax protein expression in CD4+ T cells infected with human T- cell lymphotropic virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes. Blood 95, 1386–1392.
    [Google Scholar]
  21. Hasegawa, A., Ohashi, T., Hanabuchi, S., Kato, H., Takemura, F., Masuda, T. & Kannagi, M. ( 2003; ). Expansion of human T-cell leukemia virus type 1 (HTLV-1) reservoir in orally infected rats: inverse correlation with HTLV-1-specific cellular immune response. J Virol 77, 2956–2963.[CrossRef]
    [Google Scholar]
  22. Hausmann, S., Biddison, W. E., Smith, K. J., Ding, Y. H., Garboczi, D. N., Utz, U., Wiley, D. C. & Wucherpfennig, K. W. ( 1999; ). Peptide recognition by two HLA-A2/Tax11–19-specific T cell clones in relationship to their MHC/peptide/TCR crystal structures. J Immunol 162, 5389–5397.
    [Google Scholar]
  23. Hollsberg, P. ( 1999; ). Mechanisms of T-cell activation by human T-cell lymphotropic virus type I. Microbiol Mol Biol Rev 63, 308–333.
    [Google Scholar]
  24. Iga, M., Okayama, A., Stuver, S., Matsuoka, M., Mueller, N., Aoki, M., Mitsuya, H., Tachibana, N. & Tsubouchi, H. ( 2002; ). Genetic evidence of transmission of human T cell lymphotropic virus type 1 between spouses. J Infect Dis 185, 691–695.[CrossRef]
    [Google Scholar]
  25. Igakura, T., Stinchcombe, J. C., Goon, P. K., Taylor, G. P., Weber, J. N., Griffiths, G. M., Tanaka, Y., Osame, M. & Bangham, C. R. ( 2003; ). Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton. Science 299, 1713–1716.[CrossRef]
    [Google Scholar]
  26. Jacobson, S. ( 2002; ). Immunopathogenesis of human T cell lymphotropic virus type I-associated neurologic disease. J Infect Dis 186 (Suppl. 2), S187–S192.[CrossRef]
    [Google Scholar]
  27. Jacobson, S., Shida, H., McFarlin, D. E., Fauci, A. S. & Koenig, S. ( 1990; ). Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease. Nature 348, 245–248.[CrossRef]
    [Google Scholar]
  28. Jeffery, K. J., Usuku, K., Hall, S. E. & 14 other authors ( 1999; ). HLA alleles determine human T-lymphotropic virus-I (HTLV-I) provirus load and the risk of HTLV-I-associated myelopathy. Proc Natl Acad Sci U S A 96, 3848–3853.[CrossRef]
    [Google Scholar]
  29. Jeffery, K. J., Siddiqui, A. A., Bunce, M. & 8 other authors ( 2000; ). The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type I infection. J Immunol 165, 7278–7284.[CrossRef]
    [Google Scholar]
  30. Johnson, J. M., Harrod, R. & Franchini, G. ( 2001; ). Molecular biology and pathogenesis of the human T-cell leukaemia/lymphotropic virus type I (HTLV-I). Int J Exp Pathol 82, 135–147.[CrossRef]
    [Google Scholar]
  31. Kannagi, M., Sugamura, K., Sato, H., Okochi, K., Uchino, H. & Hinuma, Y. ( 1983; ). Establishment of human cytotoxic T cell lines specific for human adult T cell leukemia virus-bearing cells. J Immunol 130, 2942–2946.
    [Google Scholar]
  32. Kannagi, M., Sugamura, K., Kinoshita, K., Uchino, H. & Hinuma, Y. ( 1984; ). Specific cytolysis of fresh tumor cells by an autologous killer T cell line derived from an adult T cell leukemia/lymphoma patient. J Immunol 133, 1037–1041.
    [Google Scholar]
  33. Kannagi, M., Harada, S., Maruyama, I. & other authors ( 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, 761–767.[CrossRef]
    [Google Scholar]
  34. Kannagi, M., Matsushita, S. & Harada, S. ( 1993; ). Expression of the target antigen for cytotoxic T lymphocytes on adult T-cell-leukemia cells. Int J Cancer 54, 582–588.[CrossRef]
    [Google Scholar]
  35. Kaplan, J. E., Litchfield, B., Rouault, C. & other authors ( 1991; ). HTLV-I-associated myelopathy associated with blood transfusion in the United States: epidemiologic and molecular evidence linking donor and recipient. Neurology 41, 192–197.[CrossRef]
    [Google Scholar]
  36. Kubota, R., Kawanishi, T., Matsubara, H., Manns, A. & Jacobson, S. ( 2000; ). HTLV-I specific IFN-γ + CD8+ lymphocytes correlate with the provirus load in peripheral blood of infected individuals. J Neuroimmunol 102, 208–215.[CrossRef]
    [Google Scholar]
  37. Lehky, T. J., Fox, C. H., Koenig, S. & 7 other authors ( 1995; ). Detection of human T-lymphotropic virus type I (HTLV-I) tax RNA in the central nervous system of HTLV-I-associated myelopathy/tropical spastic paraparesis patients by in situ hybridization. Ann Neurol 37, 167–175.[CrossRef]
    [Google Scholar]
  38. Levin, M. C., Lee, S. M., Kalume, F. & 7 other authors ( 2002; ). Autoimmunity due to molecular mimicry as a cause of neurological disease. Nat Med 8, 509–513.[CrossRef]
    [Google Scholar]
  39. Manel, N., Kinet, S., Battini, J. L., Kim, F. J., Taylor, N. & Sitbon, M. ( 2003; ). The HTLV receptor is an early T-cell activation marker whose expression requires de novo protein synthesis. Blood 101, 1913–1918.[CrossRef]
    [Google Scholar]
  40. Matsuoka, E., Takenouchi, N., Hashimoto, K. & 7 other authors ( 1998; ). Perivascular T cells are infected with HTLV-I in the spinal cord lesions with HTLV-I-associated myelopathy/tropical spastic paraparesis: double staining of immunohistochemistry and polymerase chain reaction in situ hybridization. Acta Neuropathol (Berl) 96, 340–346.[CrossRef]
    [Google Scholar]
  41. Matsuzaki, T., Nakagawa, M., Nagai, M. & 7 other authors ( 2001; ). HTLV-I provirus load correlates with progression of motor disability in HAM/TSP: analysis of 239 HAM/TSP patients including 64 patients followed up for 10 years. J Neurovirol 7, 228–234.[CrossRef]
    [Google Scholar]
  42. Moritoyo, T., Izumo, S., Moritoyo, H., Tanaka, Y., Kiyomatsu, Y., Nagai, M., Usuku, K., Sorimachi, M. & Osame, M. ( 1999; ). Detection of human T-lymphotropic virus type I p40tax protein in cerebrospinal fluid cells from patients with human T-lymphotropic virus type I-associated myelopathy/tropical spastic paraparesis. J Neurovirol 5, 241–248.[CrossRef]
    [Google Scholar]
  43. Mortreux, F., Kazanji, M., Gabet, A. S., de Thoisy, B. & Wattel, E. ( 2001; ). Two-step nature of human T-cell leukemia virus type 1 replication in experimentally infected squirrel monkeys (Saimiri sciureus). J Virol 75, 1083–1089.[CrossRef]
    [Google Scholar]
  44. Mueller, N. E. & Blattner, W. A. ( 1997; ). Retroviruses: HTLV. In Viral Infections of Humans: Epidemiology and Control, pp. 785–813. Edited by A. S. Evans & R. Kaslow. New York: Plenum.
  45. Nagai, M., Usuku, K., Matsumoto, W. & 8 other authors ( 1998; ). Analysis of HTLV-I provirus load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high provirus load strongly predisposes to HAM/TSP. J Neurovirol 4, 586–593.[CrossRef]
    [Google Scholar]
  46. 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, 50–61.[CrossRef]
    [Google Scholar]
  47. Nath, M. D., Ruscetti, F. W., Petrow-Sadowski, C. & Jones, K. S. ( 2003; ). Regulation of the cell-surface expression of an HTLV-I binding protein in human T cells during immune activation. Blood 101, 3085–3092.[CrossRef]
    [Google Scholar]
  48. Niewiesk, S., Daenke, S., Parker, C. E., Taylor, G., Weber, J., Nightingale, S. & Bangham, C. R. ( 1994; ). The transactivator gene of human T-cell leukemia virus type I is more variable within and between healthy carriers than patients with tropical spastic paraparesis. J Virol 68, 6778–6781.
    [Google Scholar]
  49. Niewiesk, S., Daenke, S., Parker, C. E., Taylor, G., Weber, J., Nightingale, S. & Bangham, C. R. ( 1995; ). Naturally occurring variants of human T-cell leukemia virus type I Tax protein impair its recognition by cytotoxic T lymphocytes and the transactivation function of Tax. J Virol 69, 2649–2653.
    [Google Scholar]
  50. Nowak, M. A. & Bangham, C. R. ( 1996; ). Population dynamics of immune responses to persistent viruses. Science 272, 74–79.[CrossRef]
    [Google Scholar]
  51. Ogg, G. S., Jin, X., Bonhoeffer, S. & 12 other authors ( 1998; ). Quantitation of HIV-1-specific cytotoxic T lymphocytes and plasma load of viral RNA. Science 279, 2103–2106.[CrossRef]
    [Google Scholar]
  52. Okochi, K. & Sato, H. ( 1984; ). Transmission of ATLV (HTLV-I) through blood transfusion. Princess Takamatsu Symp 15, 129–135.
    [Google Scholar]
  53. Overbaugh, J. & Bangham, C. R. ( 2001; ). Selection forces and constraints on retroviral sequence variation. Science 292, 1106–1109.[CrossRef]
    [Google Scholar]
  54. Pabst, R., Binns, R. M., Rothkotter, H. J. & Westermann, J. ( 1993; ). Quantitative analysis of lymphocyte fluxes in vivo. Curr Top Microbiol Immunol 184, 151–159.
    [Google Scholar]
  55. Parker, C. E., Daenke, S., Nightingale, S. & Bangham, C. R. ( 1992; ). Activated, HTLV-I-specific cytotoxic T-lymphocytes are found in healthy seropositives as well as in patients with tropical spastic paraparesis. Virology 188, 628–636.[CrossRef]
    [Google Scholar]
  56. Pique, C., Ureta-Vidal, A., Gessain, A., Chancerel, B., Gout, O., Tamouza, R., Agis, F. & Dokhelar, M. C. ( 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, 567–572.[CrossRef]
    [Google Scholar]
  57. Popovic, M., Sarin, P. S., Robert-Gurroff, M., Kalyanaraman, V. S., Mann, D., Minowada, J. & Gallo, R. C. ( 1983; ). Isolation and transmission of human retrovirus (human T-cell leukemia virus). Science 219, 856–859.[CrossRef]
    [Google Scholar]
  58. Saito, M., Taylor, G. P., Saito, A., Furukawa, Y., Usuku, K., Weber, J. N., Osame, M. & Bangham, C. R. ( 2001; ). In vivo selection of T-cell receptor junctional region sequences by HLA-A2 human T-cell lymphotropic virus type I Tax11–19 peptide complexes. J Virol 75, 1065–1071.[CrossRef]
    [Google Scholar]
  59. Schick, P., Trepel, F., Eder, M., Matzner, M., Benedek, S., Theml, H., Kaboth, W., Begemann, H. & Fliedner, T. M. ( 1975; ). Autotransfusion of 3H-cytidine-labelled blood lymphocytes in patients with Hodgkin's disease and non-Hodgkin patients. II. Exchangeable lymphocyte pools. Acta Haematol 53, 206–218.[CrossRef]
    [Google Scholar]
  60. Slattery, J. P., Franchini, G. & Gessain, A. ( 1999; ). Genomic evolution, patterns of global dissemination, and interspecies transmission of human and simian T-cell leukemia/lymphotropic viruses. Genome Res 9, 525–540.
    [Google Scholar]
  61. Smith, M. R. & Greene, W. C. ( 1990; ). Identification of HTLV-1 tax trans-activator mutants exhibiting novel transcriptional phenotypes. Genes Dev 4, 1875–1885.[CrossRef]
    [Google Scholar]
  62. Smith, R. E., Niewiesk, S., Booth, S., Bangham, C. R. & Daenke, S. ( 1997; ). Functional conservation of HTLV-1 rex balances the immune pressure for sequence variation in the rex gene. Virology 237, 397–403.[CrossRef]
    [Google Scholar]
  63. Taylor, G. P., Hall, S. E., Navarrete, S. & 9 other authors ( 1999; ). Effect of lamivudine on human T-cell leukemia virus type 1 (HTLV-1) DNA copy number, T-cell phenotype, and anti-tax cytotoxic T-cell frequency in patients with HTLV-1-associated myelopathy. J Virol 73, 10289–10295.
    [Google Scholar]
  64. Townsend, A. R., Rothbard, J., Gotch, F. M., Bahadur, G., Wraith, D. & McMichael, A. J. ( 1986; ). The epitopes of influenza nucleoprotein recognized by cytotoxic T lymphocytes can be defined with short synthetic peptides. Cell 44, 959–968.[CrossRef]
    [Google Scholar]
  65. Uchiyama, T. ( 1997; ). Human T cell leukemia virus type I (HTLV-I) and human diseases. Annu Rev Immunol 15, 15–37.[CrossRef]
    [Google Scholar]
  66. Valentin, H., Lemasson, I., Hamaia, S., Casse, H., Konig, S., Devaux, C. & Gazzolo, L. ( 1997; ). Transcriptional activation of the vascular cell adhesion molecule-1 gene in T lymphocytes expressing human T-cell leukemia virus type 1 Tax protein. J Virol 71, 8522–8530.
    [Google Scholar]
  67. Valitutti, S., Muller, S., Dessing, M. & Lanzavecchia, A. ( 1996; ). Different responses are elicited in cytotoxic T lymphocytes by different levels of T cell receptor occupancy. J Exp Med 183, 1917–1921.[CrossRef]
    [Google Scholar]
  68. Vine, A. M., Witkover, A. D., Lloyd, A. L. & 9 other authors ( 2002; ). Polygenic control of human T lymphotropic virus type I (HTLV-I) provirus load and the risk of HTLV-I-associated myelopathy/tropical spastic paraparesis. J Infect Dis 186, 932–939.[CrossRef]
    [Google Scholar]
  69. Watanabe, T. ( 1997; ). HTLV-1-associated diseases. Int J Hematol 66, 257–278.[CrossRef]
    [Google Scholar]
  70. Weidt, G., Deppert, W., Utermohlen, O., Heukeshoven, J. & Lehmann-Grube, F. ( 1995; ). Emergence of virus escape mutants after immunization with epitope vaccine. J Virol 69, 7147–7151.
    [Google Scholar]
  71. Wekerle, H., Linnington, C., Lassmann, H. & Meyermann, R. ( 1986; ). Cellular immune reactivity within the CNS. Trends Neurosci 6, 271–277.
    [Google Scholar]
  72. Westermann, J., Puskas, Z. & Pabst, R. ( 1988; ). Blood transit and recirculation kinetics of lymphocyte subsets in normal rats. Scand J Immunol 28, 203–210.[CrossRef]
    [Google Scholar]
  73. Westermann, J., Persin, S., Matyas, J., van der Meide, P. & Pabst, R. ( 1993; ). IFN-γ influences the migration of thoracic duct B and T lymphocyte subsets in vivo. Random increase in disappearance from the blood and differential decrease in reappearance in the lymph. J Immunol 150, 3843–3852.
    [Google Scholar]
  74. Wodarz, D. & Bangham, C. R. ( 2000; ). Evolutionary dynamics of HTLV-I. J Mol Evol 50, 448–455.
    [Google Scholar]
  75. Wodarz, D., Nowak, M. A. & Bangham, C. R. ( 1999; ). The dynamics of HTLV-I and the CTL response. Immunol Today 20, 220–227.[CrossRef]
    [Google Scholar]
  76. Wodarz, D., Hall, S. E., Usuku, K., Osame, M., Ogg, G. S., McMichael, A. J., Nowak, M. A. & Bangham, C. R. ( 2001; ). Cytotoxic T-cell abundance and virus load in human immunodeficiency virus type 1 and human T-cell leukaemia virus type 1. Proc R Soc Lond B Biol Sci 268, 1215–1221.[CrossRef]
    [Google Scholar]
  77. Yamamoto, N., Okada, M., Koyanagi, Y., Kannagi, M. & Hinuma, Y. ( 1982; ). Transformation of human leukocytes by cocultivation with an adult T cell leukemia virus producer cell line. Science 217, 737–739.[CrossRef]
    [Google Scholar]
  78. Yamamoto, A., Hara, H. & Kobayashi, T. ( 1997; ). Induction of the expression of gag protein in HTLV-I infected lymphocytes by anti-ICAM 1 antibody in vitro. J Neurol Sci 151, 121–126.[CrossRef]
    [Google Scholar]
  79. Yoshida, M. ( 2001; ). Multiple viral strategies of HTLV-1 for dysregulation of cell growth control. Annu Rev Immunol 19, 475–496.[CrossRef]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/vir.0.19334-0
Loading
/content/journal/jgv/10.1099/vir.0.19334-0
Loading

Data & Media loading...

Most Cited This Month

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