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Serological and Molecular Methods to Study Epidemiological Aspects of Human T-Cell Lymphotropic Virus Type 1 Infection

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1582))

Abstract

We estimated that at least 5–10 million individuals are infected with HTLV-1. Importantly, this number is based on the study of nearly 1.5 billion people living in known human T-cell lymphotropic virus type 1 (HTLV-1) endemic areas, for which reliable epidemiological data are available. However, for some highly populated regions including India, the Maghreb, East Africa, and some regions of China, no consistent data are yet available which prevents a more accurate estimation. Thus, the number of HTLV-1 infected people in the world is probably much higher. The prevalence of HTLV-1 prevalence varies depending on age, sex, and economic level in most HTLV-1 endemic areas. HTLV-1 seroprevalence gradually increases with age, especially in women. HTLV-1 has a simian origin and was originally acquired by humans through interspecies transmission from STLV-1 infected monkeys in the Old World. Three main modes of HTLV-1 transmission have been described; (1) from mother-to-child after prolonged breast-feeding lasting more than six months, (2) through sexual intercourse, which mainly, but not exclusively, occurs from male to female and lastly, (3) from contaminated blood products, which contain HTLV-1 infected lymphocytes. In specific areas, such as Central Africa, zoonotic transmission from STLV-1 infected monkeys to humans is still ongoing.

The diagnostic methods used to study the epidemiological aspects of HTLV-1 infection mainly consist of serological assays for the detection of antibodies specifically directed against different HTLV-1 antigens. Screening tests are usually based on enzyme-linked immunoabsorbent assay (ELISA), chemiluminescence enzyme-linked immunoassay (CLEIA) or particle agglutination (PA). Confirmatory tests include mostly Western blots (WB)s or innogenetics line immunoassay (INNO-LIA™) and to a lesser extent immunofluorescence assay (IFA). The search for integrated provirus in the DNA from peripheral blood cells can be performed by qualitative and/or quantitative polymerase chain reaction (qPCR). qPCR is widely used in most diagnostic laboratories and quantification of proviral DNA is useful for the diagnosis and follow-up of HTLV-1 associated diseases such as adult T-cell leukemia (ATL) and tropical spastic paraparesis/HTLV-1 associated myelopathy (TSP/HAM). PCR also provides amplicons for further sequence analysis to determine the HTLV-1 genotype present in the infected person. The use of new generation sequencing methodologies to molecularly characterize full and/or partial HTLV-1 genomic regions is increasing. HTLV-1 genotyping generates valuable molecular epidemiological data to better understand the evolutionary history of this virus.

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References

  1. Poiesz BJ, Ruscetti FW, Gazdar AF, Bunn PA, Minna JD, Gallo RC (1980) 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 77(12):7415–7419

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. (1996) Human T-cell lymphotropic viruses. IARC Monogr Eval Carcinog Risks Hum 67: 261–390

    Google Scholar 

  3. Takatsuki K, Uchiyama T, Sagawa K, Yodoi J (1977) Adult T cell leukemia in Japan. In: Seno S, Takaku F, Irino S (eds) Topics in hematology. Excerpta Medica, Amsterdam, pp 73–77

    Google Scholar 

  4. Yoshida M, Miyoshi I, Hinuma Y (1982) 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 79(6):2031–2035

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Gessain A, Barin F, Vernant JC et al (1985) Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis. Lancet 2(8452):407–410

    Article  CAS  PubMed  Google Scholar 

  6. Goncalves DU, Proietti FA, Ribas JG et al (2010) Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases. Clin Microbiol Rev 23(3):577–589

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Gessain A, Cassar O (2012) Epidemiological aspects and world distribution of HTLV-1 infection. Front Microbiol 3:388

    Article  PubMed  PubMed Central  Google Scholar 

  8. Proietti FA, Carneiro-Proietti AB, Catalan-Soares BC, Murphy EL (2005) Global epidemiology of HTLV-I infection and associated diseases. Oncogene 24(39):6058–6068

    Article  CAS  PubMed  Google Scholar 

  9. 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(4):266–281

    Article  CAS  PubMed  Google Scholar 

  10. Mueller N (1991) The epidemiology of HTLV-I infection. Cancer Causes Control 2(1):37–52

    Article  CAS  PubMed  Google Scholar 

  11. Plancoulaine S, Buigues RP, Murphy EL et al (1998) Demographic and familial characteristics of HTLV-1 infection among an isolated, highly endemic population of African origin in French Guiana. Int J Cancer 76(3):331–336

    Article  CAS  PubMed  Google Scholar 

  12. Gerard Y, Lepere JF, Pradinaud R et al (1995) Clustering and clinical diversity of adult T-cell leukemia/lymphoma associated with HTLV-I in a remote black population of French Guiana. Int J Cancer 60(6):773–776

    Article  CAS  PubMed  Google Scholar 

  13. Azarpazhooh MR, Hasanpour K, Ghanbari M et al (2012) Human T-lymphotropic virus type 1 prevalence in Northeastern Iran, Sabzevar: an epidemiologic-based study and phylogenetic analysis. AIDS Res Hum Retroviruses 28(9)

    Google Scholar 

  14. Hino S (2011) Establishment of the milk-borne transmission as a key factor for the peculiar endemicity of human T-lymphotropic virus type 1 (HTLV-1): the ATL Prevention Program Nagasaki. Proc Jpn Acad Ser B Phys Biol Sci 87(4):152–166

    Article  PubMed  PubMed Central  Google Scholar 

  15. Ureta-Vidal A, Angelin-Duclos C, Tortevoye P et al (1999) Mother-to-child transmission of human T-cell-leukemia/lymphoma virus type I: implication of high antiviral antibody titer and high proviral load in carrier mothers. Int J Cancer 82(6):832–836

    Article  CAS  PubMed  Google Scholar 

  16. Roucoux DF, Wang B, Smith D et al (2005) A prospective study of sexual transmission of human T lymphotropic virus (HTLV)-I and HTLV-II. J Infect Dis 191(9):1490–1497

    Article  PubMed  Google Scholar 

  17. Okochi K, Sato H, Hinuma Y (1984) A retrospective study on transmission of adult T cell leukemia virus by blood transfusion: seroconversion in recipients. Vox Sang 46(5):245–253

    Article  CAS  PubMed  Google Scholar 

  18. Manns A, Murphy EL, Wilks R et al (1991) Detection of early human T-cell lymphotropic virus type I antibody patterns during seroconversion among transfusion recipients. Blood 77(4):896–905

    CAS  PubMed  Google Scholar 

  19. Iwanaga M, Watanabe T, Yamaguchi K (2012) Adult T-cell leukemia: a review of epidemiological evidence. Front Microbiol 3:322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Plumelle Y, Pascaline N, Nguyen D et al (1993) Adult T-cell leukemia-lymphoma: a clinico-pathologic study of twenty-six patients from Martinique. Hematol Pathol 7(4):251–262

    CAS  PubMed  Google Scholar 

  21. Blank A, Yamaguchi K, Blank M, Zaninovic V, Sonoda S, Takatsuki K (1993) Six Colombian patients with adult T-cell leukemia/lymphoma. Leuk Lymphoma 9(4–5):407–412

    Article  CAS  PubMed  Google Scholar 

  22. Pombo-de-Oliveira MS, Carvalho SM, Borducchi D et al (2001) Adult T-cell leukemia/lymphoma and cluster of HTLV-I associated diseases in Brazilian settings. Leuk Lymphoma 42(1–2):135–144

    Article  CAS  PubMed  Google Scholar 

  23. Matutes E, Taylor GP, Cavenagh J et al (2001) Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: response and outcome in 15 patients. Br J Haematol 113(3):779–784

    Article  CAS  PubMed  Google Scholar 

  24. Gessain A, Gout O, Saal F et al (1990) Epidemiology and immunovirology of human T-cell leukemia/lymphoma virus type I-associated adult T-cell leukemia and chronic myelopathies as seen in France. Cancer Res 50(17 Suppl):5692S–5696S

    CAS  PubMed  Google Scholar 

  25. Harrington WJ Jr, Ucar A, Gill P et al (1995) Clinical spectrum of HTLV-I in south Florida. J Acquir Immune Defic Syndr Hum Retrovirol 8(5):466–473

    Article  PubMed  Google Scholar 

  26. Kirkland MA, Frasca J, Bastian I (1991) Adult T-cell leukaemia lymphoma in an aborigine. Aust N Z J Med 21(5):739–741

    Article  CAS  PubMed  Google Scholar 

  27. Einsiedel L, Cassar O, Bardy P, Kearney D, Gessain A (2013) Variant human T-cell lymphotropic virus type 1c and adult T-cell leukemia, Australia. Emerg Infect Dis 19(10):1639–1641

    Article  PubMed  PubMed Central  Google Scholar 

  28. Jogessar VB, de Bruyn CC, Bhigjee AI, Naicker VL, Bill PL, Tait D (1992) Adult T-cell leukaemia/lymphoma associated with HTLV-I in Natal. S Afr Med J 81(10):528–529

    CAS  PubMed  Google Scholar 

  29. Veelken H, Kohler G, Schneider J et al (1996) HTLV-I-associated adult T cell leukemia/lymphoma in two patients from Bucharest, Romania. Leukemia 10(8):1366–1369

    CAS  PubMed  Google Scholar 

  30. Yamaguchi K, Watanabe T (2002) Human T lymphotropic virus type-I and adult T-cell leukemia in Japan. Int J Hematol 76(Suppl 2):240–245

    Article  PubMed  Google Scholar 

  31. Gessain A, Gout O (1992) Chronic myelopathy associated with human T-lymphotropic virus type I (HTLV-I). Ann Intern Med 117(11):933–946

    Article  CAS  PubMed  Google Scholar 

  32. Gotuzzo E, Cabrera J, Deza L et al (2004) Clinical characteristics of patients in Peru with human T cell lymphotropic virus type 1-associated tropical spastic paraparesis. Clin Infect Dis 39(7):939–944

    Article  CAS  PubMed  Google Scholar 

  33. Gessain A, Gallo RC, Franchini G (1992) 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 66(4):2288–2295

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Mahieux R, Ibrahim F, Mauclere P et al (1997) 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 71(2):1317–1333

    CAS  PubMed  PubMed Central  Google Scholar 

  35. Cassar O, Capuano C, Bassot S et al (2007) Human T lymphotropic virus type 1 subtype C melanesian genetic variants of the Vanuatu Archipelago and Solomon Islands share a common ancestor. J Infect Dis 196(4):510–521

    Article  CAS  PubMed  Google Scholar 

  36. Kazanji M, Mouinga-Ondeme A, Lekana-Douki-Etenna S et al (2015) Origin of HTLV-1 in hunters of nonhuman primates in Central Africa. J Infect Dis 211(3):361–365

    Article  PubMed  Google Scholar 

  37. Filippone C, Betsem E, Tortevoye P et al (2015) A severe bite from a nonhuman primate is a major risk factor for HTLV-1 infection in hunters from Central Africa. Clin Infect Dis 60(11):1667–1676

    Article  PubMed  Google Scholar 

  38. Courouce AM, Pillonel J, Saura C (1999) Screening of blood donations for HTLV-I/II. Transfus Med Rev 13(4):267–274

    Article  CAS  PubMed  Google Scholar 

  39. Thorstensson R, Albert J, Andersson S (2002) Strategies for diagnosis of HTLV-I and -II. Transfusion 42(6):780–791

    Article  CAS  PubMed  Google Scholar 

  40. Gessain A, Dezzuti CS, Cowan EP, Lal RB (2007) Huamn T-cell lymphotropic viruses types 1 and 2. In: Murray PR, Baron EJ, Jorgensen JH, Landry ML, Pfailler MA (eds) Manual of clinical microbiology, vol 2, 9th edn. ASM Press, Washington, DC, pp 1330–1339

    Google Scholar 

  41. Lal RB (1996) Delineation of immunodominant epitopes of human T-lymphotropic virus types I and II and their usefulness in developing serologic assays for detection of antibodies to HTLV-I and HTLV-II. J Acquir Immune Defic Syndr Hum Retrovirol 13(Suppl 1):S170–S178

    Article  CAS  PubMed  Google Scholar 

  42. Parker SP, Taylor MB, Ades AE, Cubitt WD, Peckham C (1995) Use of dried blood spots for the detection and confirmation of HTLV-I specific antibodies for epidemiological purposes. J Clin Pathol 48(10):904–907

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Hogan C, Iles J, Frost EH et al (2016) Epidemic history and iatrogenic transmission of blood-borne viruses in mid-20th century Kinshasa. J Infect Dis 214(3)

    Google Scholar 

  44. Boa-Sorte N, Purificacao A, Amorim T, Assuncao L, Reis A, Galvao-Castro B (2014) Dried blood spot testing for the antenatal screening of HTLV, HIV, syphilis, toxoplasmosis and hepatitis B and C: prevalence, accuracy and operational aspects. Braz J Infect Dis 18(6):618–624

    Article  PubMed  Google Scholar 

  45. Matsubara F, Haraguchi K, Harada K, Koizumi A (2012) Screening for antibodies to human T-cell leukemia virus type I in Japanese breast milk. Biol Pharm Bull 35(5):773–776

    Article  CAS  PubMed  Google Scholar 

  46. Oelemann WM, Lowndes CM, Verissimo Da Costa GC et al (2002) Diagnostic detection of human immunodeficiency virus type 1 antibodies in urine: a brazilian study. J Clin Microbiol 40(3):881–885

    Article  PubMed  PubMed Central  Google Scholar 

  47. Miyoshi I, Sawada T, Iwahara Y, Ishii K, Kubonishi I, Taguchi H (1992) Excretion of HTLV-I in saliva. JAMA 267(2):236

    Article  CAS  PubMed  Google Scholar 

  48. Biggar RJ, Saxinger C, Gardiner C et al (1984) Type-I HTLV antibody in urban and rural Ghana, West Africa. Int J Cancer 34(2):215–219

    Article  CAS  PubMed  Google Scholar 

  49. Andersson S, Thorstensson R, Ramirez KG et al (1999) Comparative evaluation of 14 immunoassays for detection of antibodies to the human T-lymphotropic virus types I and II using panels of sera from Sweden and West Africa. Transfusion 39(8):845–851

    Article  CAS  PubMed  Google Scholar 

  50. Malm K, Kjerstadius T, Andersson S (2010) Evaluation of a new screening assay for HTLV-1 and -2 antibodies for large-scale use. J Med Virol 82(9):1606–1611

    Article  PubMed  Google Scholar 

  51. Qiu X, Hodges S, Lukaszewska T et al (2008) Evaluation of a new, fully automated immunoassay for detection of HTLV-I and HTLV-II antibodies. J Med Virol 80(3):484–493

    Article  CAS  PubMed  Google Scholar 

  52. Berini CA, Susana Pascuccio M, Bautista CT et al (2008) Comparison of four commercial screening assays for the diagnosis of human T-cell lymphotropic virus types 1 and 2. J Virol Methods 147(2):322–327

    Article  CAS  PubMed  Google Scholar 

  53. Fujino R, Kawato K, Ikeda M, Miyakoshi H, Mizukoshi M, Imai J (1991) Improvement of gelatin particle agglutination test for detection of anti-HTLV-I antibody. Jpn J Cancer Res 82(4):367–370

    Article  CAS  PubMed  Google Scholar 

  54. Ikeda M, Fujino R, Matsui T, Yoshida T, Komoda H, Imai J (1984) A new agglutination test for serum antibodies to adult T-cell leukemia virus. Gann 75(10):845–848

    CAS  PubMed  Google Scholar 

  55. Maeda Y, Imai J, Kiyokawa H, Kanamura M, Hino S (1989) Performance certification of gelatin particle agglutination assay for anti-HTLV-1 antibody: inconclusive positive results. Jpn J Cancer Res 80(10):915–919

    Article  CAS  PubMed  Google Scholar 

  56. Satake M, Yamaguchi K, Tadokoro K (2012) Current prevalence of HTLV-1 in Japan as determined by screening of blood donors. J Med Virol 84(2):327–335

    Article  PubMed  Google Scholar 

  57. Furuta RA, Ma G, Matsuoka M, Otani S, Matsukura H, Hirayama F (2015) Reevaluation of confirmatory tests for human T-cell leukemia virus Type 1 using a luciferase immunoprecipitation system in blood donors. Transfusion:880–889

    Google Scholar 

  58. Gallego S, Recalde A, Gastaldello R, Isa M, Nates S, Medeot S (1997) Kinetics study of human retrovirus antigens expression in T lymphocytic cell lines by indirect immunofluorescence assay. Viral Immunol 10(3):149–157

    Article  CAS  PubMed  Google Scholar 

  59. Gallo D, Penning LM, Hanson CV (1991) Detection and differentiation of antibodies to human T-cell lymphotropic virus types I and II by the immunofluorescence method. J Clin Microbiol 29(10):2345–2347

    CAS  PubMed  PubMed Central  Google Scholar 

  60. Mahieux R, Horal P, Mauclere P et al (2000) Human T-cell lymphotropic virus type 1 gag indeterminate western blot patterns in Central Africa: relationship to Plasmodium falciparum infection. J Clin Microbiol 38(11):4049–4057

    CAS  PubMed  PubMed Central  Google Scholar 

  61. Agbalika F, Honderlick P, Ferchal F, Perol Y (1991) Use of PCR amplification for diagnosis of HTLV-I infection after blood transfusion. Mol Cell Probes 5(5):345–349

    Article  CAS  PubMed  Google Scholar 

  62. Cesaire R, Bera O, Maier H et al (1999) Seroindeterminate patterns and seroconversions to human T-lymphotropic virus type I positivity in blood donors from Martinique, French West Indies. Transfusion 39(10):1145–1149

    Article  CAS  PubMed  Google Scholar 

  63. Gessain A, Caudie C, Gout O et al (1988) Intrathecal synthesis of antibodies to human T lymphotropic virus type I and the presence of IgG oligoclonal bands in the cerebrospinal fluid of patients with endemic tropical spastic paraparesis. J Infect Dis 157(6):1226–1234

    Article  CAS  PubMed  Google Scholar 

  64. Gallo D, Penning LM, Diggs JL, Hanson CV (1994) Sensitivities of radioimmunoprecipitation assay and PCR for detection of human T-lymphotropic type II infection. J Clin Microbiol 32(10):2464–2467

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Lillehoj EP, Alexander SS, Dubrule CJ et al (1990) Development and evaluation of a human T-cell leukemia virus type I serologic confirmatory assay incorporating a recombinant envelope polypeptide. J Clin Microbiol 28(12):2653–2658

    CAS  PubMed  PubMed Central  Google Scholar 

  66. Roberts BD, Foung SK, Lipka JJ et al (1993) Evaluation of an immunoblot assay for serological confirmation and differentiation of human T-cell lymphotropic virus types I and II. J Clin Microbiol 31(2):260–264

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Brodine SK, Kaime EM, Roberts C, Turnicky RP, Lal RB (1993) Simultaneous confirmation and differentiation of human T-lymphotropic virus types I and II infection by modified western blot containing recombinant envelope glycoproteins. Transfusion 33(11):925–929

    Article  CAS  PubMed  Google Scholar 

  68. Wiktor SZ, Alexander SS, Shaw GM et al (1990) Distinguishing between HTLV-I and HTLV-II by western blot. Lancet 335(8704):1533

    Article  CAS  PubMed  Google Scholar 

  69. Varma M, Rudolph DL, Knuchel M et al (1995) Enhanced specificity of truncated transmembrane protein for serologic confirmation of human T-cell lymphotropic virus type 1 (HTLV-1) and HTLV-2 infections by western blot (immunoblot) assay containing recombinant envelope glycoproteins. J Clin Microbiol 33(12):3239–3244

    CAS  PubMed  PubMed Central  Google Scholar 

  70. FDA US. 2014. http://www.fda.gov/BiologicsBloodVaccines/BloodBloodProducts/ApprovedProducts/LicensedProductsBLAs/BloodDonorScreening/InfectiousDisease/ucm080466.htm#anti_HTLV_Assays

    Google Scholar 

  71. CDC (1988) Licensure of screening tests for antibody to human T-lymphotropic virus type I. Morb Mortal Wkly Rep 37(736–40):45–47

    Google Scholar 

  72. CDC (1993) Recommendations for counseling persons infected with human T-lymphotrophic virus, types I and II. Centers for Disease Control and Prevention and U.S. Public Health Service Working Group. MMWR Recomm Rep 42:1–13

    Google Scholar 

  73. WHO (1990) Acquired immunodeficiency syndrome. proposed WH criteria for interpreting results from western blot assays for HIV-1, HIV-2 and HTLV-I/HTLV-II. Wkly Epidemiol Rec 65:281–283

    Google Scholar 

  74. HERN (1996) Seroepidemiology of the human T-cell leukaemia/lymphoma viruses in Europe. The HTLV European Research Network. J Acquir Immune Defic Syndr Hum Retrovirol 13(1):68–77

    Google Scholar 

  75. Zaaijer HL, Cuypers HT, Dudok de Wit C, Lelie PN (1994) Results of 1-year screening of donors in The Netherlands for human T-lymphotropic virus (HTLV) type I: significance of Western blot patterns for confirmation of HTLV infection. Transfusion 34(10):877–880

    Article  CAS  PubMed  Google Scholar 

  76. Khabbaz RF, Heneine W, Grindon A, Hartley TM, Shulman G, Kaplan J (1992) Indeterminate HTLV serologic results in U.S. blood donors: are they due to HTLV-I or HTLV-II? J Acquir Immune Defic Syndr 5(4):400–404

    CAS  PubMed  Google Scholar 

  77. Zanjani DS, Shahabi M, Talaei N, Afzalaghaee M, Tehranian F, Bazargani R (2011) Molecular analysis of human T cell lymphotropic virus type 1 and 2 (HTLV-1/2) seroindeterminate blood donors from Northeast Iran: evidence of proviral tax, env, and gag sequences. AIDS Res Hum Retroviruses 27(2):131–135

    Article  CAS  PubMed  Google Scholar 

  78. Lu SC, Chen BH (2003) Seroindeterminate HTLV-1 prevalence and characteristics in blood donors in Taiwan. Int J Hematol 77(4):412–413

    Article  PubMed  Google Scholar 

  79. Costa JM, Segurado AC (2009) Molecular evidence of human T-cell lymphotropic virus types 1 and 2 (HTLV-1 and HTLV-2) infections in HTLV seroindeterminate individuals from Sao Paulo, Brazil. J Clin Virol 44(3):185–189

    Article  CAS  PubMed  Google Scholar 

  80. Garin B, Gosselin S, de The G, Gessain A (1994) HTLV-I/II infection in a high viral endemic area of Zaire, Central Africa: comparative evaluation of serology, PCR, and significance of indeterminate western blot pattern. J Med Virol 44(1):104–109

    Article  CAS  PubMed  Google Scholar 

  81. Gessain A, Mathieux R (1995) HTLV-I “indeterminate” western blot patterns observed in sera from tropical regions: the situation revisited. J Acquir Immune Defic Syndr Hum Retrovirol 9(3):316–319

    CAS  PubMed  Google Scholar 

  82. Rouet F, Meertens L, Courouble G et al (2001) Serological, epidemiological, and molecular differences between human T-cell lymphotropic virus Type 1 (HTLV-1)-seropositive healthy carriers and persons with HTLV-I Gag indeterminate Western blot patterns from the Caribbean. J Clin Microbiol 39(4):1247–1253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. Busch MP, Switzer WM, Murphy EL, Thomson R, Heneine W (2000) Absence of evidence of infection with divergent primate T-lymphotropic viruses in United States blood donors who have seroindeterminate HTLV test results. Transfusion 40(4):443–449

    Article  CAS  PubMed  Google Scholar 

  84. Abrams A, Akahata Y, Jacobson S (2011) The prevalence and significance of HTLV-I/II seroindeterminate Western blot patterns. Viruses 3(8):1320–1331

    Article  PubMed  PubMed Central  Google Scholar 

  85. Berini CA, Eirin ME, Pando MA, Biglione MM (2007) Human Tcell lymphotropic virus types I and II (HTLV-I and -II) infection among seroindeterminate cases in Argentina. J Med Virol 79(1):69–73

    Article  CAS  PubMed  Google Scholar 

  86. Olah I, Fukumori LM, Smid J, de Oliveira AC, Duarte AJ, Casseb J (2010) Neither molecular diversity of the envelope, immunosuppression status, nor proviral load causes indeterminate HTLV western blot profiles in samples from human T-cell lymphotropic virus type 2 (HTLV-2)-infected individuals. J Med Virol 82(5):837–842

    Article  CAS  PubMed  Google Scholar 

  87. Martins ML, Santos AC, Namen-Lopes MS, Barbosa-Stancioli EF, Utsch DG, Carneiro-Proietti AB (2010) Long-term serological follow-up of blood donors with an HTLV-indeterminate western blot: antibody profile of seroconverters and individuals with false reactions. J Med Virol 82(10):1746–1753

    Article  CAS  PubMed  Google Scholar 

  88. Calattini S, Betsem E, Bassot S et al (2009) New strain of human T lymphotropic virus (HTLV) type 3 in a Pygmy from Cameroon with peculiar HTLV serologic results. J Infect Dis 199(4):561–564

    Article  PubMed  Google Scholar 

  89. Mahieux R, Gessain A (2011) HTLV-3/STLV-3 and HTLV-4 viruses: discovery, epidemiology, serology and molecular aspects. Viruses 3(7):1074–1090

    Article  PubMed  PubMed Central  Google Scholar 

  90. Wolfe ND, Heneine W, Carr JK et al (2005) Emergence of unique primate T-lymphotropic viruses among central African bushmeat hunters. Proc Natl Acad Sci U S A 102(22):7994–7999

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Calattini S, Chevalier SA, Duprez R et al (2005) Discovery of a new human T-cell lymphotropic virus (HTLV-3) in Central Africa. Retrovirology 2(1):30

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  92. Hayes CG, Burans JP, Oberst RB (1991) Antibodies to human T lymphotropic virus type I in a population from the Philippines: evidence for cross-reactivity with Plasmodium falciparum. J Infect Dis 163(2):257–262

    Article  CAS  PubMed  Google Scholar 

  93. Porter KR, Liang L, Long GW et al (1994) Evidence for anti-Plasmodium falciparum antibodies that cross-react with human T-lymphotropic virus type I proteins in a population in Irian Jaya, Indonesia. Clin Diagn Lab Immunol 1(1):11–15

    CAS  PubMed  PubMed Central  Google Scholar 

  94. Lal RB, Rudolph D, Alpers MP, Sulzer AJ, Shi YP, Lal AA (1994) Immunologic cross-reactivity between structural proteins of human T-cell lymphotropic virus type I and the blood stage of Plasmodium falciparum. Clin Diagn Lab Immunol 1(1):5–10

    CAS  PubMed  PubMed Central  Google Scholar 

  95. Jacob F, Santos-Fortuna E, Azevedo RS, Caterino-de-Araujo A (2008) Serological patterns and temporal trends of HTLV-1/2 infection in high-risk populations attending Public Health Units in Sao Paulo, Brazil. J Clin Virol 42(2):149–155

    Article  PubMed  Google Scholar 

  96. Mangano AM, Remesar M, del Pozo A, Sen L (2004) Human T lymphotropic virus types I and II proviral sequences in Argentinian blood donors with indeterminate Western blot patterns. J Med Virol 74(2):323–327

    Article  CAS  PubMed  Google Scholar 

  97. Mauclere P, Le Hesran JY, Mahieux R et al (1997) Demographic, ethnic, and geographic differences between human T cell lymphotropic virus (HTLV) type I-seropositive carriers and persons with HTLV-I Gag-indeterminate Western blots in Central Africa. J Infect Dis 176(2):505–509

    Article  CAS  PubMed  Google Scholar 

  98. Filippone C, Bassot S, Betsem E et al (2012) A new and frequent human T-cell leukemia virus indeterminate Western blot pattern: epidemiological determinants and PCR results in central African inhabitants. J Clin Microbiol 50(5):1663–1672

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Sabino EC, Zrein M, Taborda CP, Otani MM, Ribeiro-Dos-Santos G, Saez-Alquezar A (1999) Evaluation of the INNO-LIA HTLV I/II assay for confirmation of human T-cell leukemia virus-reactive sera in blood bank donations. J Clin Microbiol 37(5):1324–1328

    CAS  PubMed  PubMed Central  Google Scholar 

  100. Zrein M, Louwagie J, Boeykens H et al (1998) Assessment of a new immunoassay for serological confirmation and discrimination of human T-cell lymphotropic virus infections. Clin Diagn Lab Immunol 5(1):45–49

    CAS  PubMed  PubMed Central  Google Scholar 

  101. Caterino-de-Araujo A, Sacchi CT, Goncalves MG et al (2015) Short communication: current prevalence and risk factors associated with human T lymphotropic virus type 1 and human T lymphotropic virus type 2 infections among HIV/AIDS patients in Sao Paulo, Brazil. AIDS Res Hum Retroviruses 31(5):543–549

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Verdonck K, Gonzalez E, Maldonado F et al (2009) Comparison of three ELISAs for the routine diagnosis of human T-lymphotropic virus infection in a high-prevalence setting in Peru. Trans R Soc Trop Med Hyg 103(4):420–422

    Article  CAS  PubMed  Google Scholar 

  103. Burbelo PD, Ching KH, Mattson TL, Light JS, Bishop LR, Kovacs JA (2007) Rapid antibody quantification and generation of whole proteome antibody response profiles using LIPS (luciferase immunoprecipitation systems). Biochem Biophys Res Commun 352(4):889–895

    Article  CAS  PubMed  Google Scholar 

  104. Burbelo PD, Meoli E, Leahy HP et al (2008) Anti-HTLV antibody profiling reveals an antibody signature for HTLV-I-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Retrovirology 5:96

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  105. McMahon EJ, Fang C, Layug L, Sandler SG (1995) Pooling blood donor samples to reduce the cost of HIV-1 antibody testing. Vox Sang 68(4):215–219

    Article  CAS  PubMed  Google Scholar 

  106. Chang CS, Wu YW, Pan YC, Chen ZY, Wang CS (2002) Feasibility of human T-lymphotropic virus type I screening using pooled sera. J Formos Med Assoc 101(11):775–778

    PubMed  Google Scholar 

  107. Andersson S, Gessain A, Taylor GP (2001) Pooling of samples for seroepidemiological surveillance of human T-cell lymphotropic virus types I and II. Virus Res 78(1–2):101–106

    Article  CAS  PubMed  Google Scholar 

  108. Vandamme AM, Van Laethem K, Liu HF et al (1997) Use of a generic polymerase chain reaction assay detecting human T-lymphotropic virus (HTLV) types I, II and divergent simian strains in the evaluation of individuals with indeterminate HTLV serology. J Med Virol 52(1):1–7

    Article  CAS  PubMed  Google Scholar 

  109. Vet JA, Majithia AR, Marras SA et al (1999) Multiplex detection of four pathogenic retroviruses using molecular beacons. Proc Natl Acad Sci U S A 96(11):6394–6399

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. Heneine W, Khabbaz RF, Lal RB, Kaplan JE (1992) Sensitive and specific polymerase chain reaction assays for diagnosis of human T-cell lymphotropic virus type I (HTLV-I) and HTLV-II infections in HTLV-I/II-seropositive individuals. J Clin Microbiol 30(6):1605–1607

    CAS  PubMed  PubMed Central  Google Scholar 

  111. Liu H, Shah M, Stramer SL, Chen W, Weiblen BJ, Murphy EL (1999) Sensitivity and specificity of human T-lymphotropic virus (HTLV) types I and II polymerase chain reaction and several serologic assays in screening a population with a high prevalence of HTLV-II. Transfusion 39(11–12):1185–1193

    Article  CAS  PubMed  Google Scholar 

  112. Derse D, Heidecker G, Mitchell M, Hill S, Lloyd P, Princler G (2004) Infectious transmission and replication of human T-cell leukemia virus type 1. Front Biosci 9:2495–2499

    Article  CAS  PubMed  Google Scholar 

  113. Lins L, de Carvalho VJ, de Almeida Rego FF et al (2012) Oral health profile in patients infected with HTLV-1: clinical findings, proviral load, and molecular analysis from HTLV-1 in saliva. J Med Virol 84(9):1428–1436

    Article  CAS  PubMed  Google Scholar 

  114. Li HC, Biggar RJ, Miley WJ et al (2004) Provirus load in breast milk and risk of mother-to-child transmission of human T lymphotropic virus type I. J Infect Dis 190(7):1275–1278

    Article  PubMed  Google Scholar 

  115. Wattel E, Mariotti M, Agis F et al (1992) Quantification of HTLV-1 proviral copy number in peripheral blood of symptomless carriers from the French West Indies. J Acquir Immune Defic Syndr 5(9):943–946

    CAS  PubMed  Google Scholar 

  116. Ono A, Mochizuki M, Yamaguchi K, Miyata N, Watanabe T (1995) Increased number of circulating HTLV-1 infected cells in peripheral blood mononuclear cells of HTLV-1 uveitis patients: a quantitative polymerase chain reaction study. Br J Ophthalmol 79(3):270–276

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Feuer G, Fraser JK, Zack JA, Lee F, Feuer R, Chen IS (1996) Human T-cell leukemia virus infection of human hematopoietic progenitor cells: maintenance of virus infection during differentiation in vitro and in vivo. J Virol 70(6):4038–4044

    CAS  PubMed  PubMed Central  Google Scholar 

  118. Abbott MA, Poiesz BJ, Byrne BC, Kwok S, Sninsky JJ, Ehrlich GD (1988) Enzymatic gene amplification: qualitative and quantitative methods for detecting proviral DNA amplified in vitro. J Infect Dis 158(6):1158–1169

    Article  CAS  PubMed  Google Scholar 

  119. Lee TH, Chafets DM, Busch MP, Murphy EL (2004) Quantitation of HTLV-I and II proviral load using real-time quantitative PCR with SYBR Green chemistry. J Clin Virol 31(4):275–282

    Article  CAS  PubMed  Google Scholar 

  120. Dehee A, Cesaire R, Desire N et al (2002) Quantitation of HTLV-I proviral load by a TaqMan real-time PCR assay. J Virol Methods 102(1–2):37–51

    Article  CAS  PubMed  Google Scholar 

  121. Estes MC, Sevall JS (2003) Multiplex PCR using real time DNA amplification for the rapid detection and quantitation of HTLV I or II. Mol Cell Probes 17(2–3):59–68

    Article  CAS  PubMed  Google Scholar 

  122. Naderi M, Paryan M, Azadmanesh K, Rafatpanah H, Rezvan H, Mirab Samiee S (2012) Design and development of a quantitative real time PCR assay for monitoring of HTLV-1 provirus in whole blood. J Clin Virol 53(4):302–307

    Article  CAS  PubMed  Google Scholar 

  123. Besson G, Kazanji M (2009) One-step, multiplex, real-time PCR assay with molecular beacon probes for simultaneous detection, differentiation, and quantification of human T-cell leukemia virus types 1, 2, and 3. J Clin Microbiol 47(4):1129–1135

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Moens B, Lopez G, Adaui V et al (2009) Development and validation of a multiplex real-time PCR assay for simultaneous genotyping and human T-lymphotropic virus type 1, 2, and 3 proviral load determination. J Clin Microbiol 47(11):3682–3691

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  125. Brunetto GS, Massoud R, Leibovitch EC et al (2014) Digital droplet PCR (ddPCR) for the precise quantification of human T-lymphotropic virus 1 proviral loads in peripheral blood and cerebrospinal fluid of HAM/TSP patients and identification of viral mutations. J Neurovirol 20(4):341–351

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. Rosadas C, Puccioni-Sohler M (2015) Relevance of retrovirus quantification in cerebrospinal fluid for neurologic diagnosis. J Biomed Sci 22:66

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  127. Pinheiro LB, Coleman VA, Hindson CM et al (2012) Evaluation of a droplet digital polymerase chain reaction format for DNA copy number quantification. Anal Chem 84(2):1003–1011

    Article  CAS  PubMed  Google Scholar 

  128. Desdouits M, Cassar O, Maisonobe T et al (2013) HTLV-1-associated inflammatory myopathies: low proviral load and moderate inflammation in 13 patients from West Indies and West Africa. J Clin Virol 57(1):70–76

    Article  PubMed  Google Scholar 

  129. Nagai M, Usuku K, Matsumoto W et al (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(6):586–593

    Article  CAS  PubMed  Google Scholar 

  130. Lezin A, Olindo S, Oliere S et al (2005) Human T lymphotropic virus type I (HTLV-I) proviral load in cerebrospinal fluid: a new criterion for the diagnosis of HTLV-I-associated myelopathy/tropical spastic paraparesis? J Infect Dis 191(11):1830–1834

    Article  PubMed  Google Scholar 

  131. Takenouchi N, Yao K, Jacobson S (2004) Immunopathogensis of HTLV-I associated neurologic disease: molecular, histopathologic, and immunologic approaches. Front Biosci 9:2527–2539

    Article  CAS  PubMed  Google Scholar 

  132. Murphy EL, Lee TH, Chafets D et al (2004) Higher human T lymphotropic virus (HTLV) provirus load is associated with HTLV-I versus HTLV-II, with HTLV-II subtype A versus B, and with male sex and a history of blood transfusion. J Infect Dis 190(3):504–510

    Article  PubMed  Google Scholar 

  133. Cassar O, Einsiedel L, Afonso PV, Gessain A (2013) Human T-cell lymphotropic virus type 1 subtype C molecular variants among Indigenous Australians: new insights into the molecular epidemiology of HTLV-1 in Australo-Melanesia. PLoS Negl Trop Dis 7(9)

    Google Scholar 

  134. Komurian F, Pelloquin F, de The G (1991) In vivo genomic variability of human T-cell leukemia virus type I depends more upon geography than upon pathologies. J Virol 65(7):3770–3778

    CAS  PubMed  PubMed Central  Google Scholar 

  135. Pessoa R, Watanabe JT, Nukui Y et al (2014) Molecular characterization of human T-cell lymphotropic virus type 1 full and partial genomes by Illumina massively parallel sequencing technology. PLoS One 9(3):e93374

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  136. Yoshida M, Seiki M, Yamaguchi K, Takatsuki K (1984) Monoclonal integration of human T-cell leukemia provirus in all primary tumors of adult T-cell leukemia suggests causative role of human T-cell leukemia virus in the disease. Proc Natl Acad Sci U S A 81(8):2534–2537

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  137. Wong-Staal F, Hahn B, Manzari V et al (1983) A survey of human leukaemias for sequences of a human retrovirus. Nature 302(5909):626–628

    Article  CAS  PubMed  Google Scholar 

  138. Ikeda S, Momita S, Kinoshita K et al (1993) Clinical course of human T-lymphotropic virus type I carriers with molecularly detectable monoclonal proliferation of T lymphocytes: defining a low- and high-risk population. Blood 82(7):2017–2024

    CAS  PubMed  Google Scholar 

  139. Yamaguchi K, Seiki M, Yoshida M, Nishimura H, Kawano F, Takatsuki K (1984) The detection of human T cell leukemia virus proviral DNA and its application for classification and diagnosis of T cell malignancy. Blood 63(5):1235–1240

    CAS  PubMed  Google Scholar 

  140. Gessain A, Moulonguet I, Flageul B et al (1990) Cutaneous type of adult T cell leukemia/lymphoma in a French West Indian woman. Clonal rearrangement of T-cell receptor beta and gamma genes and monoclonal integration of HTLV-I proviral DNA in the skin infiltrate. J Am Acad Dermatol 23(5 Pt 2):994–1000

    Article  CAS  PubMed  Google Scholar 

  141. Tamiya S, Matsuoka M, Etoh K et al (1996) Two types of defective human T-lymphotropic virus type I provirus in adult T-cell leukemia. Blood 88(8):3065–3073

    CAS  PubMed  Google Scholar 

  142. Wattel E, Vartanian JP, Pannetier C, Wain-Hobson S (1995) Clonal expansion of human T-cell leukemia virus type I-infected cells in asymptomatic and symptomatic carriers without malignancy. J Virol 69(5):2863–2868

    CAS  PubMed  PubMed Central  Google Scholar 

  143. Cavrois M, Wain-Hobson S, Gessain A, Plumelle Y, Wattel E (1996) Adult T-cell leukemia/lymphoma on a background of clonally expanding human T-cell leukemia virus type-1-positive cells. Blood 88(12):4646–4650

    CAS  PubMed  Google Scholar 

  144. Cavrois M, Wain-Hobson S, Wattel E (1995) Stochastic events in the amplification of HTLV-I integration sites by linker-mediated PCR. Res Virol 146(3):179–184

    Article  CAS  PubMed  Google Scholar 

  145. Takemoto S, Matsuoka M, Yamaguchi K, Takatsuki K (1994) A novel diagnostic method of adult T-cell leukemia: monoclonal integration of human T-cell lymphotropic virus type I provirus DNA detected by inverse polymerase chain reaction. Blood 84(9):3080–3085

    CAS  PubMed  Google Scholar 

  146. Cavrois M, Gessain A, Wain-Hobson S, Wattel E (1996) Proliferation of HTLV-1 infected circulating cells in vivo in all asymptomatic carriers and patients with TSP/HAM. Oncogene 12(11):2419–2423

    CAS  PubMed  Google Scholar 

  147. Wattel E, Cavrois M, Gessain A, Wain-Hobson S (1996) Clonal expansion of infected cells: a way of life for HTLV-I. J Acquir Immune Defic Syndr Hum Retrovirol 13(Suppl 1):S92–S99

    Article  CAS  PubMed  Google Scholar 

  148. Cavrois M, Gessain A, Gout O, Wain-Hobson S, Wattel E (2000) Common human T cell leukemia virus type 1 (HTLV-1) integration sites in cerebrospinal fluid and blood lymphocytes of patients with HTLV-1-associated myelopathy/tropical spastic paraparesis indicate that HTLV-1 crosses the blood-brain barrier via clonal HTLV-1-infected cells. J Infect Dis 182(4):1044–1050

    Article  CAS  PubMed  Google Scholar 

  149. Okayama A, Stuver S, Matsuoka M et al (2004) Role of HTLV-1 proviral DNA load and clonality in the development of adult T-cell leukemia/lymphoma in asymptomatic carriers. Int J Cancer 110(4):621–625

    Article  CAS  PubMed  Google Scholar 

  150. Gabet AS, Moules V, Sibon D et al (2006) Endemic versus epidemic viral spreads display distinct patterns of HTLV-2b replication. Virology 345(1):13–21

    Article  CAS  PubMed  Google Scholar 

  151. Gabet AS, Gessain A, Wattel E (2003) High simian T-cell leukemia virus type 1 proviral loads combined with genetic stability as a result of cell-associated provirus replication in naturally infected, asymptomatic monkeys. Int J Cancer 107(1):74–83

    Article  CAS  PubMed  Google Scholar 

  152. Gillet NA, Malani N, Melamed A et al (2011) The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones. Blood 117(11):3113–3122

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  153. Berry CC, Gillet NA, Melamed A, Gormley N, Bangham CR, Bushman FD (2012) Estimating abundances of retroviral insertion sites from DNA fragment length data. Bioinformatics 28(6):755–762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  154. Melamed A, Witkover AD, Laydon DJ et al (2014) Clonality of HTLV-2 in natural infection. PLoS Pathog 10(3):e1004006

    Article  PubMed  PubMed Central  Google Scholar 

  155. Firouzi S, Lopez Y, Suzuki Y et al (2014) Development and validation of a new high-throughput method to investigate the clonality of HTLV-1-infected cells based on provirus integration sites. Genome Med 6(6):46

    Article  PubMed  PubMed Central  CAS  Google Scholar 

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Cassar, O., Gessain, A. (2017). Serological and Molecular Methods to Study Epidemiological Aspects of Human T-Cell Lymphotropic Virus Type 1 Infection. In: Casoli, C. (eds) Human T-Lymphotropic Viruses. Methods in Molecular Biology, vol 1582. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-6872-5_1

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