{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:42:14Z","timestamp":1783723334677,"version":"3.55.0"},"reference-count":101,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2019,10,23]],"date-time":"2019-10-23T00:00:00Z","timestamp":1571788800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["301869\/2017-0"],"award-info":[{"award-number":["301869\/2017-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human T-lymphotropic virus 1, a member of the Retroviridae family, causes a neglected, silent, persistent infection affecting circa 5 to 10 million people around the world, with biology, immune pathology, clinical diseases, epidemiology, and laboratory issues still unsolved. Most of the infected subjects are asymptomatic, but severe clinical disorders appear as a neurodegenerative disease (HTLV-1 associated myelopathy\u2014HAM) or a lymphoprolipherative disorder (Adult T Leukemia\/Lymphoma\u2014ATLL) and in other target organs of the human body. HTLV-1 infections are frequently asymptomatic, but there is a large spectrum of diseases that have been described along the years. The mechanisms by which the virus interacts with the host, the different modes of response of the host to the infection, and the immunogenic characteristics of the host are some of the interesting and unanswered questions that may direct the outcome of the disease. The most relevant published results dealing with the genetic variations of the host, the immune response to HTLV-1 infection, and the outcome of the infection are presented herein, including Human Leucocyte Antigen (HLA), Killer Immunoglobulin-like Receptors (KIR), interleukin 6, 10, 28, Fas and Fas ligand, IFN-gamma, TNF-A, and Mannose-binding lectin. In summary, there are still several unmet research needs in the field of useful biomarkers on HTLV-1 pathogenesis.<\/jats:p>","DOI":"10.3390\/v11110974","type":"journal-article","created":{"date-parts":[[2019,10,25]],"date-time":"2019-10-25T03:20:36Z","timestamp":1571973636000},"page":"974","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Influence of Immunogenetic Biomarkers in the Clinical Outcome of HTLV-1 Infected Persons"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1135-6507","authenticated-orcid":false,"given":"Antonio Carlos Ros\u00e1rio","family":"Vallinoto","sequence":"first","affiliation":[{"name":"Laborat\u00f3rio de Virologia, Instituto de Ci\u00eancias Biol\u00f3gica, Universidade Federal do Par\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Izaura","family":"Cayres-Vallinoto","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia, Instituto de Ci\u00eancias Biol\u00f3gica, Universidade Federal do Par\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2014-2770","authenticated-orcid":false,"given":"Maria Alice","family":"Freitas Queiroz","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia, Instituto de Ci\u00eancias Biol\u00f3gica, Universidade Federal do Par\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marlu\u00edsa de Oliveira Guimar\u00e3es","family":"Ishak","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia, Instituto de Ci\u00eancias Biol\u00f3gica, Universidade Federal do Par\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Ishak","sequence":"additional","affiliation":[{"name":"Laborat\u00f3rio de Virologia, Instituto de Ci\u00eancias Biol\u00f3gica, Universidade Federal do Par\u00e1, Bel\u00e9m 66.075-110, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1016\/S0891-5520(05)70225-7","article-title":"Human T-cell lymphotropic virus-I in Latin America","volume":"14","author":"Gotuzzo","year":"2000","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"388","DOI":"10.3389\/fmicb.2012.00388","article-title":"Epidemiological aspects and world distribution of HTLV-1 infection","volume":"3","author":"Gessain","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"934","DOI":"10.1111\/tmi.13278","article-title":"Human T-cell lymphotropic virus type 1 and associated diseases in Latin America","volume":"24","author":"Candel","year":"2019","journal-title":"Trop. Med. Int. Health"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/S0952-7915(00)00107-2","article-title":"The immune response to HTLV-I","volume":"12","author":"Bangham","year":"2000","journal-title":"Curr. Opin. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1007\/s11908-014-0459-0","article-title":"Update on neurological manifestations of HTLV-1 infection","volume":"17","author":"Araujo","year":"2015","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1146\/annurev-immunol-042617-053222","article-title":"Human T cell leukemia virus type 1: Persistence and pathogenesis","volume":"36","author":"Bangham","year":"2018","journal-title":"Annu. Rev. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1031","DOI":"10.1016\/S0140-6736(86)91298-5","article-title":"Htlv-I associated myelopathy, a new clinical entity","volume":"327","author":"Osame","year":"1986","journal-title":"Lancet"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1093\/cid\/ciy289","article-title":"Early juvenile human T-cell lymphotropic virus type-1-associated myelopathy\/tropical spastic paraparesis: Study of 25 patients","volume":"67","author":"Varandas","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"890","DOI":"10.1093\/clinids\/12.5.890","article-title":"Tropical neuromyelopathies and retroviruses: A review","volume":"12","author":"Bucher","year":"1990","journal-title":"Rev. Infect. Dis."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1086\/506365","article-title":"Natural history of viral markers in children infected with human T lymphotropic virus type I in Jamaica","volume":"194","author":"Maloney","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12977-015-0236-7","article-title":"Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients","volume":"13","author":"Cook","year":"2016","journal-title":"Retrovirology"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"449","DOI":"10.3389\/fmicb.2018.00449","article-title":"HTLV-1: Regulating the balance between proviral latency and reactivation","volume":"9","author":"Kulkarni","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2","DOI":"10.1097\/NEN.0000000000000141","article-title":"Visualization of HTLV-1-specific cytotoxic T lymphocytes in the spinal cords of patients with HTLV-1-associated myelopathy\/tropical spastic paraparesis","volume":"74","author":"Matsuura","year":"2015","journal-title":"J. Neuropathol. Exp. Neurol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ijid.2019.05.010","article-title":"Cognitive impairment in HTLV-1-associated myelopathy, proviral load and inflammatory markers","volume":"84","author":"Champs","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"6035","DOI":"10.1038\/sj.onc.1208970","article-title":"Cellular immune response to HTLV-1","volume":"24","author":"Bangham","year":"2005","journal-title":"Oncogene"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3960\/jslrt.50.1","article-title":"HTLV-1 and the host immune system: How the virus disrupts immune regulation, leading to HTLV-1 associated diseases","volume":"50","author":"Satou","year":"2010","journal-title":"J. Clin. Exp. Hematopathol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1186\/1742-4690-2-16","article-title":"Discovery of adult T-cell leukemia","volume":"2","author":"Takatsuki","year":"2005","journal-title":"Retrovirology"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1220","DOI":"10.1016\/S0140-6736(87)91362-6","article-title":"T-lymphocyte alveolitis in HTLV-I-associated myelopathy","volume":"330","author":"Sugimoto","year":"1987","journal-title":"Lancet"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2483","DOI":"10.1182\/blood-2010-11-321364","article-title":"Effects of valproate on Tax and HBZ expression in HTLV-1 and HAM\/TSP T lymphocytes","volume":"118","author":"Belrose","year":"2011","journal-title":"Blood"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2615","DOI":"10.3389\/fmicb.2017.02615","article-title":"HTLV-1 HBZ viral protein: A key player in HTLV-1 mediated diseases","volume":"8","author":"Baratella","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1136\/bjophthalmol-2017-310658","article-title":"Systemic diseases in patients with HTLV-1-associated uveitis","volume":"102","author":"Nakao","year":"2018","journal-title":"Br. J. Ophthalmol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/S0042-6822(02)00091-0","article-title":"Human T cell leukemia virus type I-induced disease: Pathways to cancer and neurodegeneration","volume":"308","author":"Barmak","year":"2003","journal-title":"Virology"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"323","DOI":"10.3389\/fmicb.2012.00323","article-title":"The roles of acquired and innate immunity in human T-cell leukemia virus type 1-mediated diseases","volume":"3","author":"Kannagi","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"S119","DOI":"10.1097\/00042560-199600001-00020","article-title":"Immunogenetics of HTLV-I\/II and associated diseases","volume":"13","author":"Sonoda","year":"1996","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"617","DOI":"10.1093\/jnci\/90.8.617","article-title":"Human leukocyte antigen class II alleles associated with human T-cell lymphotropic virus type I infection and adult T-cell leukemia\/lymphoma in a black population","volume":"90","author":"Manns","year":"1998","journal-title":"J. Natl. Cancer Inst."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3848","DOI":"10.1073\/pnas.96.7.3848","article-title":"HLA alleles determine human T-lymphotropic virus-I (HTLV-I) proviral load and the risk of HTLV-I-associated myelopathy","volume":"96","author":"Jeffery","year":"1999","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"7278","DOI":"10.4049\/jimmunol.165.12.7278","article-title":"The influence of HLA class I alleles and heterozygosity on the outcome of human T cell lymphotropic virus type I infection","volume":"165","author":"Jeffery","year":"2000","journal-title":"J. Immunol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"6086","DOI":"10.1128\/JVI.75.13.6086-6094.2001","article-title":"Free major histocompatibility complex class I heavy chain is preferentially targeted for degradation by human T-cell leukemia\/lymphotropic virus type 1 p12(I) protein","volume":"75","author":"Johnson","year":"2001","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"880","DOI":"10.1086\/314917","article-title":"Polymorphism of the 5\u2032-flanking region of the tumor necrosis factor (TNF)-alpha gene and susceptibility to human T-cell lymphotropic virus type I (HTLV-I) uveitis","volume":"180","author":"Seki","year":"1999","journal-title":"J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1262","DOI":"10.1016\/S0198-8859(00)00182-8","article-title":"Tumor necrosis factor, tumor necrosis factor receptors type 1 and 2, lymphotoxin-\u03b1, and HLA-DRB1 gene polymorphisms in human T-Cell lymphotropic virus type I associated myelopathy","volume":"61","author":"Nishimura","year":"2000","journal-title":"Hum. Immunol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1182\/blood.V97.4.987","article-title":"Existence of escape mutant in HTLV-I tax during the development of adult T-cell leukemia","volume":"97","author":"Furukawa","year":"2001","journal-title":"Blood"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1047","DOI":"10.1089\/088922201300343735","article-title":"HLA-A*26, HLA-B*4002, HLA-B*4006, and HLA-B*4801 alleles predispose to adult T cell leukemia: The limited recognition of HTLV type 1 tax peptide anchor motifs and epitopes to generate anti-HTLV type 1 tax CD8(+) cytotoxic T lymphocytes","volume":"17","author":"Yashiki","year":"2001","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"773","DOI":"10.1099\/vir.0.80509-0","article-title":"Differences in viral and host genetic risk factors for development of human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy\/tropical spastic paraparesis between Iranian and Japanese HTLV-1-infected individuals","volume":"86","author":"Sabouri","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1002\/ijc.22767","article-title":"Risk of human T-lymphotropic virus type I-associated diseases in Jamaica with common HLA types","volume":"121","author":"Goedert","year":"2007","journal-title":"Int. J. Cancer"},{"key":"ref_35","first-page":"94","article-title":"Association between HLA-DRB1*01 and HLA-Cw*08 and outcome following HTLV-I infection","volume":"4","author":"Rafatpanah","year":"2007","journal-title":"Iran. J. Immunol."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Macnamara, A., Rowan, A., Hilburn, S., Kadolsky, U., Fujiwara, H., Suemori, K., Yasukawa, M., Taylor, G., Bangham, C.R., and Asquith, B. (2010). HLA class I binding of HBZ determines outcome in HTLV-1 infection. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001117"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"804","DOI":"10.1016\/j.humimm.2010.05.011","article-title":"Role of killer cell immunoglobulin-like receptor gene content and human leukocyte antigen-C group in susceptibility to human T-lymphotropic virus 1-associated myelopathy\/tropical spastic paraparesis in Peru","volume":"71","author":"Talledo","year":"2010","journal-title":"Hum. Immunol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1089\/aid.2010.0165","article-title":"HLA-G 14-bp insertion\/deletion polymorphism is a risk factor for HTLV-1 infection","volume":"27","author":"Haddad","year":"2011","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2551","DOI":"10.1007\/s00415-013-7014-z","article-title":"Association between HLA alleles and HAM\/TSP in individuals infected with HTLV-1","volume":"260","author":"Vicario","year":"2013","journal-title":"J. Neurol."},{"key":"ref_40","first-page":"264","article-title":"Association between HLA class I alleles and proviral load in HTLV-I associated myelopathy\/tropical spastic paraperesis (HAM\/TSP) patients in Iranian population","volume":"16","author":"Taghaddosi","year":"2013","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2742","DOI":"10.1099\/jgv.0.000559","article-title":"HLA-G 3\u2032-untranslated region polymorphisms are associated with HTLV-1 infection, proviral load and HTLV-associated myelopathy\/tropical spastic paraparesis development","volume":"97","author":"Haddad","year":"2016","journal-title":"J. Gen. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virusres.2016.11.009","article-title":"The effect of HTLV-1 virulence factors (HBZ, Tax, proviral load), HLA class I and plasma neopterin on manifestation of HTLV-1 associated myelopathy tropical spastic paraparesis","volume":"228","author":"Tarokhian","year":"2017","journal-title":"Virus Res."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.virusres.2017.11.010","article-title":"Polymorphisms in HLA-C and KIR alleles are not associated with HAM\/TSP risk in HTLV-1-infected subjects","volume":"244","author":"Assone","year":"2018","journal-title":"Virus Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"eaao2892","DOI":"10.1126\/sciimmunol.aao2892","article-title":"Inhibitory killer cell immunoglobulin-like receptors strengthen CD8(+) T cell-mediated control of HIV-1, HCV, and HTLV-1","volume":"3","author":"Boelen","year":"2018","journal-title":"Sci. Immunol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Al Basatena, N.K.S., Macnamara, A., Vine, A.M., Thio, C.L., Astemborski, J., Usuku, K., Osame, M., Kirk, G.D., Donfield, S.M., and Goedert, J.J. (2011). KIR2DL2 enhances protective and detrimental HLA class I-mediated immunity in chronic viral infection. PLoS Pathog., 7.","DOI":"10.1371\/journal.ppat.1002270"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.humimm.2012.05.006","article-title":"In contrast to HIV, KIR3DS1 does not influence outcome in HTLV-1 retroviral infection","volume":"73","author":"Olavarria","year":"2012","journal-title":"Hum. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1761","DOI":"10.1086\/522966","article-title":"Ex vivo analysis of human T lymphotropic virus type 1-specific CD4+ cells by use of a major histocompatibility complex class II tetramer composed of a neurological disease-susceptibility allele and its immunodominant peptide","volume":"196","author":"Nose","year":"2007","journal-title":"J. Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1186\/1742-4690-6-19","article-title":"In vivo expression of the HBZ gene of HTLV-1 correlates with proviral load, inflammatory markers and disease severity in HTLV-1 associated myelopathy\/tropical spastic paraparesis (HAM\/TSP)","volume":"6","author":"Saito","year":"2009","journal-title":"Retrovirology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1111\/j.1365-2567.2010.03398.x","article-title":"Structure\/function of human killer cell immunoglobulin-like receptors: Lessons from polymorphisms, evolution, crystal structures and mutations","volume":"132","author":"Campbell","year":"2011","journal-title":"Immunology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1016\/j.smim.2008.10.002","article-title":"The genetic and evolutionary balances in human NK cell receptor diversity","volume":"20","author":"Parham","year":"2008","journal-title":"Semin. Immunol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3969","DOI":"10.4049\/jimmunol.180.6.3969","article-title":"Synergistic polymorphism at two positions distal to the ligand-binding site makes KIR2DL2 a stronger receptor for HLA-C than KIR2DL3","volume":"180","author":"Moesta","year":"2008","journal-title":"J. Immunol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/S0198-8859(02)00419-6","article-title":"Association between interleukin-6 gene polymorphism and human T-cell leukemia virus type I associated myelopathy","volume":"63","author":"Nishimura","year":"2002","journal-title":"Hum. Immunol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1089\/vim.2016.0152","article-title":"IL17A polymorphism is not associated with human T-lymphotropic virus 1-associated myelopathy\/tropical spastic paraparesis","volume":"30","author":"Neco","year":"2017","journal-title":"Viral Immunol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"795","DOI":"10.3389\/fmicb.2018.00795","article-title":"IFNG +874A\/T polymorphism among asymptomatic HTLV-1-infected individuals is potentially related to a worse prognosis","volume":"9","author":"Queiroz","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1111\/j.1399-0039.2012.01887.x","article-title":"Interleukin-18 and interferon-gamma polymorphisms are implicated on proviral load and susceptibility to human T-lymphotropic virus type 1 infection","volume":"80","author":"Haddad","year":"2012","journal-title":"Tissue Antigens"},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Schor, D., Porto, L.C., Roma, E.H., Quintana, M.S.B., Fabricio-Silva, G.M., Bonecini-Almeida, M.G., Araujo, A.Q., and Andrada-Serpa, M.J. (2018). Lack of association between single-nucleotide polymorphisms of pro- and anti-inflammatory cytokines and HTLV-1-associated myelopathy\/tropical spastic paraparesis development in patients from Rio de Janeiro, Brazil. BMC Infect. Dis., 18.","DOI":"10.1186\/s12879-018-3510-1"},{"key":"ref_57","first-page":"3770","article-title":"Tumor necrosis factor alpha polymorphism associated with increased susceptibility to development of adult T-cell leukemia\/lymphoma in human T-lymphotropic virus type 1 carriers","volume":"61","author":"Tsukasaki","year":"2001","journal-title":"Cancer Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.je.2016.08.017","article-title":"Interactions between inflammatory gene polymorphisms and HTLV-I infection for total death, incidence of cancer, and atherosclerosis-related diseases among the Japanese population","volume":"27","author":"Kairupan","year":"2017","journal-title":"J. Epidemiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1279","DOI":"10.1086\/423942","article-title":"Polymorphism in the interleukin-10 promoter affects both provirus load and the risk of human T lymphotropic virus type I-associated myelopathy\/tropical spastic paraparesis","volume":"190","author":"Sabouri","year":"2004","journal-title":"J. Infect. Dis."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2141","DOI":"10.1002\/jmv.21341","article-title":"Correlation between polymorphisms at interleukin-6 but not at interleukin-10 promoter and the risk of human T lymphotropic virus type I-associated myelopathy\/tropical spastic paraparesis in Brazilian individuals","volume":"80","author":"Gadelha","year":"2008","journal-title":"J. Med. Virol."},{"key":"ref_61","first-page":"258","article-title":"Association of IL-10 gene polymorphisms and human T lymphotropic virus type I-associated myelopathy\/tropical spastic paraparesis in North-East of Iran (Mashhad)","volume":"16","author":"Shirdel","year":"2013","journal-title":"Iran. J. Basic Med. Sci."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"e20180481","DOI":"10.1590\/0037-8682-0481-2018","article-title":"Polymorphism in the interleukin-10 gene is associated with overactive bladder phenotype associated with HTLV-1 infection","volume":"52","author":"Braz","year":"2019","journal-title":"Rev. Soc. Bras. Med. Trop."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1186\/1743-422X-9-40","article-title":"Paradoxical expression of IL-28B mRNA in peripheral blood in human T-cell leukemia virus type-1 mono-infection and co-infection with hepatitis C virus","volume":"9","author":"Kamihira","year":"2012","journal-title":"Virol. J."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1093\/cid\/cis343","article-title":"Development of tropical spastic paraparesis in human T-lymphotropic virus type 1 carriers is influenced by interleukin 28B gene polymorphisms","volume":"55","author":"Lopez","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_65","doi-asserted-by":"crossref","unstructured":"Sanabani, S.S., Nukui, Y., Pereira, J., da Costa, A.C., de Oliveira, A.C., Pessoa, R., Leal, F.E., Segurado, A.C., Kallas, E.G., and Sabino, E.C. (2012). Lack of evidence to support the association of a single IL28B genotype SNP rs12979860 with the HTLV-1 clinical outcomes and proviral load. BMC Infect. Dis., 12.","DOI":"10.1186\/1471-2334-12-374"},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Assone, T., de Souza, F.V., Gaester, K.O., Fonseca, L.A., Odo, C.L., Malta, F., Pinho, J.R., Fde, T.G., Duarte, A.J., and de Oliveira, A.C. (2014). IL28B gene polymorphism SNP rs8099917 genotype GG is associated with HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) in HTLV-1 carriers. PLoS Negl. Trop. Dis., 8.","DOI":"10.1371\/journal.pntd.0003199"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/j.cyto.2015.11.004","article-title":"IL28B gene polymorphisms and Th1\/Th2 cytokine levels might be associated with HTLV-associated arthropathy","volume":"77","author":"Santana","year":"2016","journal-title":"Cytokine"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1189\/jlb.0407198","article-title":"Fas 670 promoter polymorphism is associated to susceptibility, clinical presentation, and survival in adult T cell leukemia","volume":"83","author":"Farre","year":"2008","journal-title":"J. Leukoc. Biol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.virusres.2011.09.015","article-title":"FAS-670A\/G single nucleotide polymorphism may be associated with human T lymphotropic virus-1 infection and clinical evolution to TSP\/HAM","volume":"163","author":"Vallinoto","year":"2012","journal-title":"Virus Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"726","DOI":"10.1002\/jmv.24681","article-title":"The FAS-670 AA genotype is associated with high proviral load in peruvian HAM\/TSP patients","volume":"89","author":"Rosado","year":"2017","journal-title":"J. Med. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1426423","DOI":"10.1080\/2162402X.2018.1426423","article-title":"A genetic IFN\/STAT1\/FAS axis determines CD4 T stem cell memory levels and apoptosis in healthy controls and adult T-cell leukemia patients","volume":"7","author":"Khouri","year":"2018","journal-title":"Oncoimmunology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/S0198-8859(02)00829-7","article-title":"Influence of cytokine and mannose binding protein gene polymorphisms on human t-cell leukemia virus type I (HTLV-I) provirus load in HTLV-I asymptomatic carriers","volume":"64","author":"Nishimura","year":"2003","journal-title":"Hum. Immunol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1016\/j.humimm.2005.06.006","article-title":"Characterization of mannose-binding lectin gene polymorphism among human T-cell lymphotropic virus 1 and 2-infected asymptomatic subjects","volume":"66","author":"Pontes","year":"2005","journal-title":"Hum. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1590\/S0074-02762007000800015","article-title":"Polymorphism in the promoter region of the mannose-binding lectin gene among human T-cell lymphotropic virus infected subjects","volume":"102","author":"Alves","year":"2007","journal-title":"Mem. Inst. Oswaldo Cruz"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1111\/j.1365-3083.2009.02291.x","article-title":"The elevated interferon gamma production is an important immunological marker in HAM\/TSP pathogenesis","volume":"70","author":"Montanheiro","year":"2009","journal-title":"Scand. J. Immunol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.micpath.2015.11.018","article-title":"Correlation between clinical symptoms and peripheral immune response in HAM\/TSP","volume":"92","author":"Sousa","year":"2016","journal-title":"Microb. Pathog."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1134","DOI":"10.1089\/aid.2016.0296","article-title":"Mediators go together: High production of CXCL9, CXCL10, IFN-gamma, and TNF-alpha in HTLV-1-associated myelopathy\/tropical spastic paraparesis","volume":"33","author":"Neco","year":"2017","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"9589","DOI":"10.1073\/pnas.0501794102","article-title":"IL-6 trans-signaling via STAT3 directs T cell infiltration in acute inflammation","volume":"102","author":"McLoughlin","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1086\/508783","article-title":"Haplotypes of IL6 and IL10 and susceptibility to human T lymphotropic virus type I infection among children","volume":"194","author":"Brown","year":"2006","journal-title":"J. Infect. Dis."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"119","DOI":"10.3389\/fimmu.2017.00119","article-title":"Interferon lambda: Modulating immunity in infectious diseases","volume":"8","author":"Syedbasha","year":"2017","journal-title":"Front. Immunol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Tarokhian, H., Rahimi, H., Mosavat, A., Shirdel, A., Rafatpanah, H., Akbarin, M.M., Bari, A., Ramezani, S., and Rezaee, S.A. (2018). HTLV-1-host interactions on the development of adult T cell leukemia\/lymphoma: Virus and host gene expressions. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-5209-5"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1159\/000490058","article-title":"Interferon Lambda Family along with HTLV-1 Proviral Load, Tax, and HBZ Implicated in the Pathogenesis of Myelopathy\/Tropical Spastic Paraparesis","volume":"18","author":"Mozhgani","year":"2018","journal-title":"Neurodegener. Dis."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1080\/01926230701320337","article-title":"Apoptosis: A review of programmed cell death","volume":"35","author":"Elmore","year":"2007","journal-title":"Toxicol. Pathol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.cellsig.2003.08.007","article-title":"Death receptor-induced cell killing","volume":"16","author":"Thorburn","year":"2004","journal-title":"Cell Signal."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"869","DOI":"10.1007\/s10495-007-0748-2","article-title":"Mitochondrial carriers and pores: Key regulators of the mitochondrial apoptotic program?","volume":"12","author":"Schwarz","year":"2007","journal-title":"Apoptosis"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3237","DOI":"10.1038\/sj.onc.1202581","article-title":"Caspases: The proteases of the apoptotic pathway","volume":"17","author":"Nunez","year":"1998","journal-title":"Oncogene"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"R97","DOI":"10.1016\/S1074-5521(98)90615-9","article-title":"Caspases: Key mediators of apoptosis","volume":"5","author":"Thornberry","year":"1998","journal-title":"Chem. Biol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0092-8674(91)90614-5","article-title":"The polypeptide encoded by the cDNA for human cell surface antigen Fas can mediate apoptosis","volume":"66","author":"Itoh","year":"1991","journal-title":"Cell"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"10709","DOI":"10.1016\/S0021-9258(19)50076-X","article-title":"Purification and molecular cloning of the APO-1 cell surface antigen, a member of the tumor necrosis factor\/nerve growth factor receptor superfamily. Sequence identity with the Fas antigen","volume":"267","author":"Oehm","year":"1992","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1016\/S0161-5890(97)00081-3","article-title":"Identification and characterisation of polymorphisms in the promoter region of the human Apo-1\/Fas (CD95) gene","volume":"34","author":"Huang","year":"1997","journal-title":"Mol. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"645","DOI":"10.1093\/rheumatology\/38.7.645","article-title":"Evaluation of a new Apo-1\/Fas promoter polymorphism in rheumatoid arthritis and systemic lupus erythematosus patients","volume":"38","author":"Huang","year":"1999","journal-title":"Rheumatology (Oxf.)"},{"key":"ref_92","first-page":"2397","article-title":"Fas and Fas ligand gene polymorphisms in primary Sjogren\u2019s syndrome","volume":"27","author":"Bolstad","year":"2000","journal-title":"J. Rheumatol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1038\/sj.cdd.4400964","article-title":"Genetic polymorphisms of Fas (CD95) and FasL (CD178) in human longevity: Studies on centenarians","volume":"9","author":"Pinti","year":"2002","journal-title":"Cell Death Differ."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5596","DOI":"10.1158\/1078-0432.CCR-05-1739","article-title":"Polymorphisms of FAS and FAS ligand genes involved in the death pathway and risk and progression of squamous cell carcinoma of the head and neck","volume":"12","author":"Zhang","year":"2006","journal-title":"Clin. Cancer Res."},{"key":"ref_95","first-page":"97","article-title":"A fashi lymphoproliferative phenotype reveals non-apoptotic fas signaling in HTLV-1-associated neuroinflammation","volume":"8","author":"Menezes","year":"2017","journal-title":"Front. Microbiol."},{"key":"ref_96","first-page":"255","article-title":"HTLV-I induced myeloneuropathy in WKAH rats: Apoptosis and local activation of the HTLV-I pX and TNF-alpha genes implicated in the pathogenesis","volume":"11","author":"Ohya","year":"1997","journal-title":"Leukemia"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"2685","DOI":"10.3389\/fmicb.2017.02685","article-title":"Family aggregation of HTLV-1 infection associated with FAS -670A\/G polymorphism: A case report","volume":"8","author":"Vallinoto","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0161-5890(01)00038-4","article-title":"The mannan-binding lectin pathway of complement activation: Biology and disease association","volume":"38","author":"Petersen","year":"2001","journal-title":"Mol. Immunol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1016\/S0006-291X(03)01543-2","article-title":"The genetic background as a determinant of human T-cell leukemia virus type 1 proviral load","volume":"309","author":"Nitta","year":"2003","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"1829","DOI":"10.1002\/jmv.23656","article-title":"Mannose binding lectin and mannose binding lectin-associated serine protease-2 genes polymorphisms in human T-lymphotropic virus infection","volume":"85","author":"Coelho","year":"2013","journal-title":"J. Med. Virol."},{"key":"ref_101","first-page":"85","article-title":"Evaluation of Annexin 1 as a clinical prognosis biomarker in HTLV-1 infection. In: XIV International Symposium on HTLV in Brazil","volume":"47","author":"Santana","year":"2018","journal-title":"Rev. Patol. Trop."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/11\/974\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:28:39Z","timestamp":1760189319000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/11\/974"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,10,23]]},"references-count":101,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2019,11]]}},"alternative-id":["v11110974"],"URL":"https:\/\/doi.org\/10.3390\/v11110974","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,10,23]]}}}