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PMID: 10365395 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Review

Genetic control and dynamics of the cellular immune response to the human T-cell leukaemia virus, HTLV-I.

Philosophical transactions of the Royal Society of London. Series B, Biological sciences ·Vol. 354 ·No. 1384 ·1999-04-29 ·Pages 691-700

Bangham CR, Hall SE, Jeffery KJ, Vine AM, Witkover A, Nowak MA, Wodarz D, Usuku K, Osame M

Abstract

About 1% of people infected with the human T-cell leukaemia virus, type 1 (HTLV-I) develop a disabling chronic inflammatory disease of the central nervous system known as HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Patients with HAM/TSP have a vigorous immune response to HTLV-I, and it has been widely suggested that this immune response, particularly the HTLV-I-specific cytotoxic T-lymphocyte (CTL) response, causes the tissue damage that is seen in HAM/TSP. In this paper we summarize recent evidence that a strong CTL response to HTLV-I does in fact protect against HAM/TSP by reducing the proviral load of HTLV-I. We conclude that HTLV-I is persistently replicating at a high level, despite the relative constancy of its genome sequence. These results imply that antiretroviral drugs could reduce the risk of HAM/TSP by reducing the viral load, and that an effective anti-HTLV-I vaccine should elicit a strong CTL response to the virus. The dynamic nature of the infection also has implications for the epidemiology and the evolution of HTLV-I.

MeSH Terms
Human T-lymphotropic virus 1/genetics,immunology,physiology Humans Paraparesis, Tropical Spastic/epidemiology,immunology Risk Factors T-Lymphocytes, Cytotoxic/immunology Viral Load Virus Replication
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Bangham C R
Department of Immunology, Imperial College School of Medicine, London, UK. c.bangham@ic.ac.uk
Hall S E
Jeffery K J
Vine A M
Witkover A
Nowak M A
Wodarz D
Usuku K
Osame M
References (66)
66 references, click to expand
  1. Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis.
    Lancet. 1985 Aug 24;2(8452):407-10 PMID: 2863442
  2. HTLV-I associated myelopathy, a new clinical entity.
    Lancet. 1986 May 3;1(8488):1031-2 PMID: 2871307
  3. Intrafamilial transmission of adult T cell leukemia virus.
    J Infect Dis. 1986 Nov;154(5):851-7 PMID: 2877031
  4. Identification of point mutations in the envelope gene of Moloney murine leukemia virus TB temperature-sensitive paralytogenic mutant ts1: molecular determinants for neurovirulence.
    J Virol. 1988 Jan;62(1):357-60 PMID: 3334748
  5. Genetic and environmental influences on premature death in adult adoptees.
    N Engl J Med. 1988 Mar 24;318(12):727-32 PMID: 3347221
  6. Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions.
    Mol Biol Evol. 1986 Sep;3(5):418-26 PMID: 3444411
  7. Spontaneous proliferation of peripheral blood lymphocytes increased in patients with HTLV-I-associated myelopathy.
    Neurology. 1988 Aug;38(8):1302-7 PMID: 2899862
  8. Human T cell leukemia viruses use a receptor determined by human chromosome 17.
    Science. 1988 Dec 16;242(4885):1557-9 PMID: 3201246
  9. Chronic inflammatory arthropathy associated with HTLV-I.
    Lancet. 1989 Feb 25;1(8635):441 PMID: 2563817
  10. Retrovirus-induced murine motor neuron disease: mapping the determinant of spongiform degeneration within the envelope gene.
    Proc Natl Acad Sci U S A. 1989 May;86(10):3896-900 PMID: 2542954
  11. Increased replication of HTLV-I in HTLV-I-associated myelopathy.
    Ann Neurol. 1989 Sep;26(3):331-5 PMID: 2802532
  12. HTLV-1 and polymyositis in Jamaica.
    Lancet. 1989 Nov 18;2(8673):1184-7 PMID: 2572904
  13. High human T-cell lymphotropic virus type I proviral DNA load with polyclonal integration in peripheral blood mononuclear cells of French West Indian, Guianese, and African patients with tropical spastic paraparesis.
    Blood. 1990 Jan 15;75(2):428-33 PMID: 1967218
  14. Association of a particular amino acid sequence of the HLA-DR beta 1 chain with HTLV-I-associated myelopathy.
    Eur J Immunol. 1990 Jul;20(7):1603-6 PMID: 2387316
  15. In vivo cellular tropism of human T-cell leukemia virus type 1.
    J Virol. 1990 Nov;64(11):5682-7 PMID: 1976827
  16. Infective dermatitis of Jamaican children: a marker for HTLV-I infection.
    Lancet. 1990 Dec 1;336(8727):1345-7 PMID: 1978165
  17. Circulating CD8+ cytotoxic T lymphocytes specific for HTLV-I pX in patients with HTLV-I associated neurological disease.
    Nature. 1990 Nov 15;348(6298):245-8 PMID: 2146511
  18. Molecular evolution of human T-cell leukemia virus.
    J Mol Evol. 1990 Dec;31(6):493-9 PMID: 2176698
  19. Increased HTLV-I proviral DNA in HTLV-I-associated myelopathy: a quantitative polymerase chain reaction study.
    Ann Neurol. 1991 Feb;29(2):194-201 PMID: 2012389
  20. Common west African HLA antigens are associated with protection from severe malaria.
    Nature. 1991 Aug 15;352(6336):595-600 PMID: 1865923
  21. Presence of HTLV-I proviral DNA in central nervous system of patients with HTLV-I-associated myelopathy.
    Ann Neurol. 1992 Jan;31(1):39-45 PMID: 1543349
  22. T-cell activation by autologous human T-cell leukemia virus type I-infected T-cell clones.
    Proc Natl Acad Sci U S A. 1992 Mar 15;89(6):2110-4 PMID: 1549569
  23. Target epitope in the Tax protein of human T-cell leukemia virus type I recognized by class I major histocompatibility complex-restricted cytotoxic T cells.
    J Virol. 1992 May;66(5):2928-33 PMID: 1373197
  24. Search for human T-cell leukemia virus type I (HTLV-I) proviral sequences by polymerase chain reaction in the central nervous system tissue of HTLV-I-associated myelopathy.
    Arch Virol. 1992;124(1-2):31-43 PMID: 1571019
  25. Activated, HTLV-1-specific cytotoxic T-lymphocytes are found in healthy seropositives as well as in patients with tropical spastic paraparesis.
    Virology. 1992 Jun;188(2):628-36 PMID: 1374983
  26. Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I).
    Ann Intern Med. 1992 Dec 1;117(11):933-46 PMID: 1443956
  27. Fluctuation of HTLV-I proviral DNA in peripheral blood mononuclear cells of HTLV-I-associated myelopathy.
    J Neuroimmunol. 1993 Feb;42(2):147-54 PMID: 8429100
  28. Mother-to-child transmission of human T-lymphotropic virus type I (HTLV-I): an extended follow-up study on children between 18 and 22-24 years old in Okinawa, Japan.
    Int J Cancer. 1993 Feb 20;53(4):597-600 PMID: 8436432
  29. An HTLV-I vaccine: why, how, for whom?
    AIDS Res Hum Retroviruses. 1993 May;9(5):381-6 PMID: 8318266
  30. Immunocytochemical analysis of the cellular infiltrate in the spinal cord lesions in HTLV-I-associated myelopathy.
    J Neuropathol Exp Neurol. 1993 Jul;52(4):424-30 PMID: 8355031
  31. Human T-cell leukaemia virus type I and neurological disease.
    Curr Opin Neurobiol. 1993 Oct;3(5):773-8 PMID: 8260828
  32. Human T cell leukemia virus type I infection and chronic myelopathy.
    Brain Pathol. 1993 Jan;3(1):1-10 PMID: 8269079
  33. Circulating anti-Tax cytotoxic T lymphocytes from human T-cell leukemia virus type I-infected people, with and without tropical spastic paraparesis, recognize multiple epitopes simultaneously.
    J Virol. 1994 May;68(5):2860-8 PMID: 7512153
  34. An autoaggressive process against bystander tissues in HTLV-I-infected individuals: a possible pathomechanism of HAM/TSP.
    Med Hypotheses. 1993 Dec;41(6):542-7 PMID: 8183132
  35. Do T cells cause HTLV-1-associated disease?: a taxing problem.
    Clin Exp Immunol. 1994 May;96(2):179-81 PMID: 8187324
  36. Expression of human T lymphotropic virus type 1 (HTLV-1) tax/rex gene in fresh bronchoalveolar lavage cells of HTLV-1-infected individuals.
    Clin Exp Immunol. 1994 May;96(2):193-201 PMID: 7910532
  37. Functional consequences of mutations in HIV-1 Gag p55 selected by CTL pressure.
    Virology. 1994 Aug 15;203(1):101-5 PMID: 8030265
  38. Detection of human T lymphotrophic virus type I (HTLV-I) proviral DNA and analysis of T cell receptor V beta CDR3 sequences in spinal cord lesions of HTLV-I-associated myelopathy/tropical spastic paraparesis.
    J Exp Med. 1994 Sep 1;180(3):831-9 PMID: 8064235
  39. T-cell-mediated immunopathology versus direct cytolysis by virus: implications for HIV and AIDS.
    Immunol Today. 1994 Jun;15(6):262-8 PMID: 7915115
  40. The transactivator gene of human T-cell leukemia virus type I is more variable within and between healthy carriers than patients with tropical spastic paraparesis.
    J Virol. 1994 Oct;68(10):6778-81 PMID: 8084014
  41. Viral dynamics in human immunodeficiency virus type 1 infection.
    Nature. 1995 Jan 12;373(6510):117-22 PMID: 7529365
  42. Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection.
    Nature. 1995 Jan 12;373(6510):123-6 PMID: 7816094
  43. 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. 1995 Feb;37(2):167-75 PMID: 7847858
  44. Immunopathological mechanisms of human T cell lymphotropic virus type 1 (HTLV-I) uveitis. Detection of HTLV-I-infected T cells in the eye and their constitutive cytokine production.
    J Clin Invest. 1995 Feb;95(2):852-8 PMID: 7860769
  45. 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. 1995 Apr;69(4):2649-53 PMID: 7533860
  46. High activated and memory cytotoxic T-cell responses to HTLV-1 in healthy carriers and patients with tropical spastic paraparesis.
    Virology. 1996 Mar 1;217(1):139-46 PMID: 8599198
  47. Population dynamics of immune responses to persistent viruses.
    Science. 1996 Apr 5;272(5258):74-9 PMID: 8600540
  48. Evolution in a chronic RNA virus infection: selection on HTLV-I tax protein differs between healthy carriers and patients with tropical spastic paraparesis.
    J Mol Evol. 1996 Apr;42(4):452-8 PMID: 8642614
  49. Human T-lymphotropic virus type I-associated myelopathy and tax gene expression in CD4+ T lymphocytes.
    Ann Neurol. 1996 Jul;40(1):84-90 PMID: 8687197
  50. Phenotypic analysis of antigen-specific T lymphocytes.
    Science. 1996 Oct 4;274(5284):94-6 PMID: 8810254
  51. The main HTLV-I-harboring cells in the muscles of viral carriers with polymyositis are not macrophages but CD4+ lymphocytes.
    Acta Neuropathol. 1996 Oct;92(4):358-61 PMID: 8891067
  52. Human T-cell lymphotropic virus type 1 (HTLV-1)-induced syncytium formation mediated by vascular cell adhesion molecule-1: evidence for involvement of cell adhesion molecules in HTLV-1 biology.
    J Virol. 1997 Feb;71(2):1173-80 PMID: 8995639
  53. HTLV-I-associated myelopathy: analysis of 213 patients based on clinical features and laboratory findings.
    J Neurovirol. 1995 Mar;1(1):50-61 PMID: 9222342
  54. Human T cell leukemia virus type I (HTLV-I)-specific CD8+ CTL clones from patients with HTLV-I-associated neurologic disease secrete proinflammatory cytokines, chemokines, and matrix metalloproteinase.
    J Immunol. 1997 Aug 15;159(4):2018-25 PMID: 9257869
  55. Human CD4+ T lymphocytes recognize a highly conserved epitope of human T lymphotropic virus type 1 (HTLV-1) env gp21 restricted by HLA DRB1*0101.
    Clin Exp Immunol. 1998 Feb;111(2):278-85 PMID: 9486393
  56. Analysis of HTLV-I proviral load in 202 HAM/TSP patients and 243 asymptomatic HTLV-I carriers: high proviral load strongly predisposes to HAM/TSP.
    J Neurovirol. 1998 Dec;4(6):586-93 PMID: 10065900
  57. CLINICAL AND PATHOLOGICAL OBSERVATIONS ON JAMAICAN NEUROPATHY; A REPORT ON 206 CASES.
    Brain. 1964 Sep;87:425-62 PMID: 14215171
  58. POLYMORPHISM AND NATURAL SELECTION IN HUMAN POPULATIONS.
    Cold Spring Harb Symp Quant Biol. 1964;29:137-49 PMID: 14278460
  59. Restriction of in vitro T cell-mediated cytotoxicity in lymphocytic choriomeningitis within a syngeneic or semiallogeneic system.
    Nature. 1974 Apr 19;248(5450):701-2 PMID: 4133807
  60. Adult T-cell leukemia: clinical and hematologic features of 16 cases.
    Blood. 1977 Sep;50(3):481-92 PMID: 301762
  61. Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma.
    Proc Natl Acad Sci U S A. 1980 Dec;77(12):7415-9 PMID: 6261256
  62. Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera.
    Proc Natl Acad Sci U S A. 1981 Oct;78(10):6476-80 PMID: 7031654
  63. Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease.
    Proc Natl Acad Sci U S A. 1982 Mar;79(6):2031-5 PMID: 6979048
  64. Establishment of human cytotoxic T cell lines specific for human adult T cell leukemia virus-bearing cells.
    J Immunol. 1983 Jun;130(6):2942-6 PMID: 6189906
  65. 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. 1983 Jun;80(12):3618-22 PMID: 6304725
  66. Rates of evolution of the retroviral oncogene of Moloney murine sarcoma virus and of its cellular homologues.
    Proc Natl Acad Sci U S A. 1985 Jun;82(12):4198-201 PMID: 2987967
Article Info
Journal
Philosophical transactions of the Royal Society of London. Series B, Biological sciences
Abbr.
Philos Trans R Soc Lond B Biol Sci
ISSN
0962-8436
DOI
10.1098/rstb.1999.0422
Email
c.bangham@ic.ac.uk
Published
1999-04-29
Pages
691-700
Language
English
Region
England
NLM ID
7503623
PMCID
PMC1692558
Subset
IM
Grants
Wellcome Trust · United Kingdom
External Links
PubMed source DOI: 10.1098/rstb.1999.0422 PMC Full Text View journal details
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