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Abstract

Human T-lymphotropic virus type 1 (HTLV-1) provirus expression is mainly directed by Tax-responsive elements (TRE) within the long terminal repeats (LTR). Mutations in TRE can reduce provirus expression and since a high proviral load (PVL) is a risk factor for the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), we evaluated polymorphisms in the 5′ LTR and the association with PVL and disease progression. HTLV-1 LTR and sequences derived from asymptomatic carriers (AC) and HAM/TSP patients followed in a longitudinal study were analysed according to PVL and clinical severity. Individuals infected with HTLV-1 presenting the canonical TRE, considering strain ATK-1 as the consensus, displayed sustained higher PVL. By contrast, an LTR A125G mutation in TRE was associated with slightly reduced PVL only in HAM/TSP patients, although it did not influence the speed of disease progression. Moreover, this polymorphism was frequent in Latin American strains of the HTLV-1 Cosmopolitan Transcontinental subtype. Therefore, polymorphisms in the 5′ TRE of HTLV-1 may represent one of the factors influencing PVL in HAM/TSP patients, especially in the Latin American population. Indeed, higher PVL in the peripheral blood has been associated with an increased inflammatory activity in the spinal cord and to a poorer prognosis in HAM/TSP. However, this event was not associated with TRE polymorphisms.

Funding
This study was supported by the:
  • Fundação Oswaldo Cruz
    • Principle Award Recipient: NotApplicable
  • Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
    • Principle Award Recipient: YagoCôrtes Pinheiro Gomes
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2021-09-08
2021-09-23
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References

  1. Hinuma Y, Nagata K, Hanaoka M, Nakai M, Matsumoto T. 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; 78:6476–6480 [View Article] [PubMed]
    [Google Scholar]
  2. Hinuma Y, Komoda H, Chosa T, Kondo T, Kohakura M. Antibodies to adult T-cell leukemia-virus-associated antigen (ATLA) in sera from patients with ATL and controls in Japan: a nation-wide sero-epidemiologic study. Int J Cancer 1982; 29:631–635 [View Article] [PubMed]
    [Google Scholar]
  3. Osame M, Usuku K, Izumo S, Ijichi N, Amitani H. HTLV-I associated myelopathy, a new clinical entity. The Lancet 1986; 1:1031–1032 [View Article]
    [Google Scholar]
  4. Gessain A, Cassar O. Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol 2012; 3:388 [View Article] [PubMed]
    [Google Scholar]
  5. Daenke S, Nightingale S, Cruickshank JK, Bangham CR. Sequence variants of human T-cell lymphotropic virus type I from patients with tropical spastic paraparesis and adult T-cell leukemia do not distinguish neurological from leukemic isolates. J Virol 1990; 64:1278–1282 [View Article] [PubMed]
    [Google Scholar]
  6. Gessain A, Gallo RC, Franchini G. Low degree of human T-cell leukemia/lymphoma virus type I genetic drift in vivo as a means of monitoring viral transmission and movement of ancient human populations. J Virol 1992; 66:2288–2295 [View Article] [PubMed]
    [Google Scholar]
  7. Wattel E, Vartanian JP, Pannetier C, Wain-Hobson S. Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy. J Virol 1995; 69:2863–2868 [View Article] [PubMed]
    [Google Scholar]
  8. Umeki K, Hisada M, Maloney EM, Hanchard B, Okayama A. Proviral loads and clonal expansion of HTLV-1-infected cells following vertical transmission: a 10-year follow-up of children in Jamaica. Intervirology 2009; 52:115–122 [View Article] [PubMed]
    [Google Scholar]
  9. Espíndola OM, Oliveira LC, Ferreira PMS, Leite A, Lima M. High IFN-γ/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 2015; 58:106–114 [View Article] [PubMed]
    [Google Scholar]
  10. Gillet NA, Malani N, Melamed A, Gormley N, Carter R. The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones. Blood 2011; 117:3113–3122 [View Article] [PubMed]
    [Google Scholar]
  11. Mahieux R, Ibrahim F, Mauclere P, Herve V, Michel P. Molecular epidemiology of 58 new African human T-cell leukemia virus type 1 (HTLV-1) strains: identification of a new and distinct HTLV-1 molecular subtype in Central Africa and in Pygmies. J Virol 1997; 71:1317–1333 [View Article] [PubMed]
    [Google Scholar]
  12. Vandamme AM, Salemi M, Desmyter J. The simian origins of the pathogenic human T-cell lymphotropic virus type I. Trends Microbiol 1998; 6:477–483 [View Article] [PubMed]
    [Google Scholar]
  13. Wolfe ND, Heneine W, Carr JK, Garcia AD, Shanmugam V. Emergence of unique primate T-lymphotropic viruses among central African bushmeat hunters. Proc Natl Acad Sci U S A 2005; 102:7994–7999 [View Article] [PubMed]
    [Google Scholar]
  14. Van Dooren S, Gotuzzo E, Salemi M, Watts D, Audenaert E. Evidence for a post-Columbian introduction of human T-cell lymphotropic virus [type I] [corrected] in Latin America. J Gen Virol 1998; 79:2695–2708 [View Article] [PubMed]
    [Google Scholar]
  15. Kashima S, Alcantara LC, Takayanagui OM, Cunha MAV, Castro BG. Distribution of human T cell lymphotropic virus type 1 (HTLV-1) subtypes in Brazil: genetic characterization of LTR and tax region. AIDS Res Hum Retroviruses 2006; 22:953–959 [View Article] [PubMed]
    [Google Scholar]
  16. Kannian P, Green PL. Human T Lymphotropic Virus Type 1 (HTLV-1): molecular biology and oncogenesis. Viruses 2010; 2:2037–2077 [View Article] [PubMed]
    [Google Scholar]
  17. Lemasson I, Polakowski NJ, Laybourn PJ, Nyborg JK. Transcription factor binding and histone modifications on the integrated proviral promoter in human T-cell leukemia virus-I-infected T-cells. J Biol Chem 2002; 277:49459–49465 [View Article] [PubMed]
    [Google Scholar]
  18. de la Fuente C, Kashanchi F. The expanding role of Tax in transcription. Retrovirology 2004; 1:19 [View Article] [PubMed]
    [Google Scholar]
  19. Beimling P, Moelling K. Direct interaction of CREB protein with 21 bp Tax-response elements of HTLV-ILTR. Oncogene 1992; 7:257–262 [PubMed]
    [Google Scholar]
  20. Giam CZ, Xu YL. HTLV-I tax gene product activates transcription via pre-existing cellular factors and camp responsive element. J Biol Chem 1989; 264:15236–15241 [PubMed]
    [Google Scholar]
  21. Giebler HA, Loring JE, van Orden K, Colgin MA, Garrus JE. Anchoring of CREB binding protein to the human T-cell leukemia virus type 1 promoter: a molecular mechanism of Tax transactivation. Mol Cell Biol 1997; 17:5156–5164 [View Article] [PubMed]
    [Google Scholar]
  22. Currer R, Van Duyne R, Jaworski E, Guendel I, Sampey G. HTLV tax: a fascinating multifunctional co-regulator of viral and cellular pathways. Front Microbiol 2012; 3:406 [View Article] [PubMed]
    [Google Scholar]
  23. Azran I, Schavinsky-Khrapunsky Y, Aboud M. Role of Tax protein in human T-cell leukemia virus type-I leukemogenicity. Retrovirology 2004; 1:20 [View Article] [PubMed]
    [Google Scholar]
  24. Fujisawa J, Seiki M, Sato M, Yoshida M. A transcriptional enhancer sequence of HTLV-I is responsible for trans-activation mediated by p40 chi HTLV-I. EMBO J 1986; 5:713–718 [PubMed]
    [Google Scholar]
  25. Montagne J, Béraud C, Crenon I, Lombard-Platet G, Gazzolo L. Tax1 induction of the HTLV-I 21 bp enhancer requires cooperation between two cellular DNA-binding proteins. EMBO J 1990; 9:957–964 [PubMed]
    [Google Scholar]
  26. Nagai M, Usuku K, Matsumoto W, Kodama D, Takenouchi N. 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; 4:586–593 [View Article] [PubMed]
    [Google Scholar]
  27. Silva MTT, Harab RC, Leite AC, Schor D, Araújo A. Human T Lymphotropic Virus Type 1 (HTLV-1) Proviral Load in Asymptomatic Carriers, HTLV-1–Associated Myelopathy/Tropical Spastic Paraparesis, and Other Neurological Abnormalities Associated with HTLV-1 Infection. Clin Infect Dis 2007; 44:689–692 [View Article] [PubMed]
    [Google Scholar]
  28. Lima M, Bica R, Araujo A. Gender influence on the progression of HTLV-I associated myelopathy/tropical spastic paraparesis. J Neurol Neurosurg Psychiatry 2005; 76:294–296 [View Article] [PubMed]
    [Google Scholar]
  29. Liu HF, Vandamme AM, Kazadi K, Carton H, Desmyter J. Familial transmission and minimal sequence variability of human T-lymphotropic virus type I (HTLV-I) in Zaire. AIDS Res Hum Retroviruses 1994; 10:1135–1142 [View Article] [PubMed]
    [Google Scholar]
  30. Hall TA. BioEdit: a user-friendly biological sequence alignment editor and analysis program for Windows 95/98/NT. Nucleic Acids Symp Ser 1999; 41:95–98
    [Google Scholar]
  31. Kumar S, Stecher G, Li M, Knyaz C, Tamura K. mega X: Molecular Evolutionary Genetics Analysis across Computing Platforms. Mol Biol Evol 2018; 35:1547–1549 [View Article] [PubMed]
    [Google Scholar]
  32. Magri MC, Brigido LF de M, Rodrigues R, Morimoto HK, Caterino-de-Araujo A. Tax gene characterization of human t-lymphotropic virus type 1 strains from brazilian hiv-coinfected patients. AIDS Res Hum Retroviruses 2012; 28: [View Article]
    [Google Scholar]
  33. Yoshida M. Discovery of HTLV-1, the first human retrovirus, its unique regulatory mechanisms, and insights into pathogenesis. Oncogene 2005; 24:5931–5937 [View Article] [PubMed]
    [Google Scholar]
  34. Araujo AQ, Silva MTT. The HTLV-1 neurological complex. Lancet Neurol 2006; 5:1068–1076 [View Article] [PubMed]
    [Google Scholar]
  35. Bangham CRM, Araujo A, Yamano Y, Taylor GP. HTLV-1-associated myelopathy/tropical spastic paraparesis. Nat Rev Dis Primer 2015; 1:1–17
    [Google Scholar]
  36. Lepoutre V, Jain P, Quann K, Wigdahl B, Khan ZK. Role of resident CNS cell populations in HTLV-1-associated neuroinflammatory disease. Front Biosci (Landmark Ed) 2009; 14:1152–1168 [View Article] [PubMed]
    [Google Scholar]
  37. Niederer HA, Laydon DJ, Melamed A, Elemans M, Asquith B. HTLV-1 proviral integration sites differ between asymptomatic carriers and patients with HAM/TSP. Virol J 2014; 11:172 [View Article] [PubMed]
    [Google Scholar]
  38. Jeffery KJ, Usuku K, Hall SE, Matsumoto W, Taylor GP. HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy. Proc Natl Acad Sci U S A 1999; 96:3848–3853 [View Article] [PubMed]
    [Google Scholar]
  39. Asquith B, Zhang Y, Mosley AJ, de Lara CM, Wallace DL. In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection. Proc Natl Acad Sci U S A 2007; 104:8035–8040 [View Article] [PubMed]
    [Google Scholar]
  40. Asquith B, Bangham CRM. How does HTLV-I persist despite a strong cell-mediated immune response?. Trends Immunol 2008; 29:4–11 [View Article] [PubMed]
    [Google Scholar]
  41. Macnamara A, Rowan A, Hilburn S, Kadolsky U, Fujiwara H. HLA class I binding of HBZ determines outcome in HTLV-1 infection. PLoS Pathog 2010; 6:e1001117 [View Article] [PubMed]
    [Google Scholar]
  42. Catalan-Soares BC, Carneiro-Proietti ABF, Da Fonseca FG, Correa-Oliveira R, Peralva-Lima D. HLA class I alleles in HTLV-1-associated myelopathy and asymptomatic carriers from the Brazilian cohort GIPH. Med Microbiol Immunol 2009; 198:1–3 [View Article]
    [Google Scholar]
  43. Borducchi DM, Gerbase-DeLima M, Morgun A, Shulzhenko N, Pombo-de-Oliveira MS. Human leucocyte antigen and human T-cell lymphotropic virus type 1 associated diseases in Brazil. Br J Haematol 2003; 123:954–955 [View Article] [PubMed]
    [Google Scholar]
  44. Neto WK, Da-Costa AC, de Oliveira ACS, Martinez VP, Nukui Y. Correlation between LTR point mutations and proviral load levels among human T cell lymphotropic virus type 1 (HTLV-1) asymptomatic carriers. Virol J 2011; 8:535 [View Article] [PubMed]
    [Google Scholar]
  45. Boxus M, Twizere J-C, Legros S, Dewulf J-F, Kettmann R et al. The HTLV-1 tax interactome. Retrovirology 2008; 5:76 [View Article] [PubMed]
    [Google Scholar]
  46. Jin DY, Jeang KT. HTLV-I Tax self-association in optimal trans-activation function. Nucleic Acids Res 1997; 25:379–387 [View Article] [PubMed]
    [Google Scholar]
  47. Merezak C, Pierreux C, Adam E, Lemaigre F, Rousseau GG. Suboptimal enhancer sequences are required for efficient bovine leukemia virus propagation in vivo: implications for viral latency. J Virol 2001; 75:6977–6988 [View Article] [PubMed]
    [Google Scholar]
  48. Rego FF de A, de Oliveira T, Giovanetti M, Galvão-Castro B, Gonçalves M de S. Deep sequencing analysis of human T cell lymphotropic virus type 1 long terminal repeat 5’ region from patients with tropical spastic paraparesis/human T cell lymphotropic virus type 1-associated myelopathy and asymptomatic carriers. AIDS Res Hum Retroviruses 2016; 32:279–283 [View Article] [PubMed]
    [Google Scholar]
  49. Terme J-M, Wencker M, Favre-Bonvin A, Bex F, Gazzolo L et al. Cross talk between expression of the human T-cell leukemia virus type 1 Tax transactivator and the oncogenic bHLH transcription factor TAL1. J Virol 2008; 82:7913–7922 [View Article] [PubMed]
    [Google Scholar]
  50. Terme J-M, Calvignac S, Duc Dodon M, Gazzolo L, Jordan A. E Box motifs as mediators of proviral latency of human retroviruses. Retrovirology 2009; 6:81 [View Article] [PubMed]
    [Google Scholar]
  51. Furukawa Y, Yamashita M, Usuku K, Izumo S, Nakagawa M. 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 2000; 182:1343–1349 [View Article] [PubMed]
    [Google Scholar]
  52. Bandeira LM, Uehara SNO, Puga MAM, Rezende GR, Vicente ACP. HTLV-1 intrafamilial transmission among Japanese immigrants in Brazil. J Med Virol 2018; 90:351–357 [View Article] [PubMed]
    [Google Scholar]
  53. Bangham CRM, Osame M. Cellular immune response to HTLV-1. Oncogene 2005; 24:6035–6046 [View Article] [PubMed]
    [Google Scholar]
  54. Sato T, Coler-Reilly A, Utsunomiya A, Araya N, Yagishita N. CSF CXCL10, CXCL9, and neopterin as candidate prognostic biomarkers for HTLV-1-associated myelopathy/tropical spastic paraparesis. PLoS Negl Trop Dis 2013; 7:e2479 [View Article] [PubMed]
    [Google Scholar]
  55. Sato T, Yagishita N, Tamaki K, Inoue E, Hasegawa D. Proposal of Classification Criteria for HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis Disease Activity. Front Microbiol 2018; 9:1651 [View Article] [PubMed]
    [Google Scholar]
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