{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T09:11:50Z","timestamp":1778922710416,"version":"3.51.4"},"reference-count":128,"publisher":"Public Library of Science (PLoS)","issue":"4","license":[{"start":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T00:00:00Z","timestamp":1617321600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Human T-cell leukemia virus type 1 (HTLV-1) was the first oncogenic human retrovirus identified in humans which infects at least 10\u201315 million people worldwide. Large HTLV-1 endemic areas exist in Southern Japan, the Caribbean, Central and South America, the Middle East, Melanesia, and equatorial regions of Africa. HTLV-1 TAX viral protein is thought to play a critical role in HTLV-1 associated diseases. We have used numerous bio-informatics and immuno-informatics implements comprising sequence and construction tools for the construction of a 3D model and epitope prediction for HTLV-1 Tax viral protein. The conformational linear B-cell and T-cell epitopes for HTLV-1 TAX viral protein have been predicted for their possible collective use as vaccine candidates. Based on in silico investigation two B cell epitopes, KEADDNDHEPQISPGGLEPPSEKHFR and DGTPMISGPCPKDGQPS spanning from 324\u2013349 and 252\u2013268 respectively; and T cell epitopes, LLFGYPVYV, ITWPLLPHV and GLLPFHSTL ranging from 11\u201319, 163\u2013171 and 233\u2013241 were found most antigenic and immunogenic epitopes. Among different vaccine constructs generated by different combinations of these epitopes our predicted vaccine construct was found to be most antigenic with a score of 0.57. T cell epitopes interacted strongly with HLA-A*0201 suggesting a significant immune response evoked by these epitopes. Molecular docking study also showed a high binding affinity of the vaccine construct for TLR4. The study was carried out to predict antigenic determinants of the Tax protein along with the 3D protein modeling. The study revealed a potential multi epitope vaccine that can raise the desired immune response against HTLV-1 and be useful in developing effective vaccines against Human T-lymphotropic virus.<\/jats:p>","DOI":"10.1371\/journal.pone.0248001","type":"journal-article","created":{"date-parts":[[2021,4,2]],"date-time":"2021-04-02T17:23:07Z","timestamp":1617384187000},"page":"e0248001","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":27,"title":["Epitope-based universal vaccine for Human T-lymphotropic virus-1 (HTLV-1)"],"prefix":"10.1371","volume":"16","author":[{"given":"Md. Thosif","family":"Raza","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4958-2537","authenticated-orcid":true,"given":"Shagufta","family":"Mizan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhana","family":"Yasmin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0680-1936","authenticated-orcid":true,"given":"Al-Shahriar","family":"Akash","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1433-5085","authenticated-orcid":true,"given":"Shah 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Sciences"},{"issue":"3","key":"pone.0248001.ref003","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1093\/oxfordjournals.molbev.a026317","article-title":"Tempo and mode of human and simian T-lymphotropic virus (HTLV\/STLV) evolution revealed by analyses of full-genome sequences","volume":"17","author":"M Salemi","year":"2000","journal-title":"Molecular Biology and Evolution"},{"issue":"3","key":"pone.0248001.ref004","first-page":"131","article-title":"Origin and evolution of human and simian T-cell lymphotropic viruses","volume":"1","author":"M Salemi","year":"1999","journal-title":"AIDS Rev"},{"issue":"6","key":"pone.0248001.ref005","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1101\/gr.9.6.525","article-title":"Genomic evolution, patterns of global dissemination, and interspecies transmission of human and simian T-cell leukemia\/lymphotropic viruses","volume":"9","author":"JP Slattery","year":"1999","journal-title":"Genome research"},{"issue":"12","key":"pone.0248001.ref006","doi-asserted-by":"crossref","first-page":"10316","DOI":"10.1128\/JVI.72.12.10316-10322.1998","article-title":"Simian T-cell lymphotropic virus type 1 from Mandrillus sphinx as a simian counterpart of human T-cell lymphotropic virus type 1 subtype D","volume":"72","author":"R Mahieux","year":"1998","journal-title":"Journal of virology"},{"issue":"2","key":"pone.0248001.ref007","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1099\/vir.0.19630-0","article-title":"Identification in gelada baboons (Theropithecus gelada) of a distinct simian T-cell lymphotropic virus type 3 with a broad range of Western blot reactivity","volume":"85","author":"S Van Dooren","year":"2004","journal-title":"Journal of general virology"},{"issue":"3","key":"pone.0248001.ref008","first-page":"163","article-title":"Epidemiology, origin and genetic diversity of HTLV-1 retrovirus and STLV-1 simian affiliated retrovirus","volume":"93","author":"A Gessain","year":"2000","journal-title":"Bulletin de la Societe de Pathologie Exotique (1990)"},{"issue":"9","key":"pone.0248001.ref009","doi-asserted-by":"crossref","first-page":"4700","DOI":"10.1128\/JVI.78.9.4700-4709.2004","article-title":"Simian T-cell leukemia virus (STLV) infection in wild primate populations in Cameroon: evidence for dual STLV type 1 and type 3 infection in agile mangabeys (Cercocebus agilis)","volume":"78","author":"V Courgnaud","year":"2004","journal-title":"Journal of virology"},{"issue":"1","key":"pone.0248001.ref010","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1128\/JVI.76.1.259-268.2002","article-title":"Complete sequence of a novel highly divergent simian T-cell lymphotropic virus from wild-caught red-capped mangabeys (Cercocebus torquatus) from Cameroon: a new primate T-lymphotropic virus type 3 subtype","volume":"76","author":"L Meertens","year":"2002","journal-title":"Journal of virology"},{"issue":"7","key":"pone.0248001.ref011","doi-asserted-by":"crossref","first-page":"2848","DOI":"10.1073\/pnas.91.7.2848","article-title":"A primate T-lymphotropic virus, PTLV-L, different from human T-lymphotropic viruses types I and II, in a wild-caught baboon (Papio hamadryas)","volume":"91","author":"P Goubau","year":"1994","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"30","key":"pone.0248001.ref012","first-page":"4","article-title":"Discovery of a new human T-cell lymphotropic virus (HTLV-3) in Central Africa","volume":"2","author":"S Calattini","year":"2005","journal-title":"Retrovirology"},{"key":"pone.0248001.ref013","doi-asserted-by":"crossref","first-page":"6058","DOI":"10.1038\/sj.onc.1208968","article-title":"Global epidemiology of HTLV-I infection and associated diseases","volume":"24","author":"FA Proietti","year":"2005","journal-title":"Oncogene"},{"key":"pone.0248001.ref014","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1128\/CMR.00063-09","article-title":"Epidemiology, treatment, and prevention of human T-cell leukemia virus type 1-associated diseases","volume":"23","author":"DU Gon\u00e7alves","year":"2010","journal-title":"Clin. Microbiol. Rev"},{"issue":"8801","key":"pone.0248001.ref015","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/0140-6736(92)90699-4","article-title":"HTLV-I and uveitis","volume":"339","author":"M Mochizuki","year":"1992","journal-title":"The Lancet"},{"issue":"2","key":"pone.0248001.ref016","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1136\/bjo.75.2.76","article-title":"Seroprevalence of antibodies to HTLV-I in patients with ocular disorders","volume":"75","author":"K Nakao","year":"1991","journal-title":"British journal of ophthalmology"},{"key":"pone.0248001.ref017","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1182\/blood.V66.1.120.120","article-title":"Preleukemic state of adult T cell leukemia: abnormal T lymphocytosis induced by human adult T cell leukemia-lymphoma virus","volume":"66","author":"K Kinoshita","year":"1985","journal-title":"Blood"},{"issue":"5","key":"pone.0248001.ref018","first-page":"684","article-title":"Development of adult T-cell leukemia-lymphoma (ATL) in two anti-ATL-associated antigen-positive healthy adults","volume":"73","author":"K Kinoshita","year":"1982","journal-title":"Gann"},{"key":"pone.0248001.ref019","first-page":"325","article-title":"Adult T-cell leukemia-lymphoma in Kagoshima district, southwestern Japan: clinical and hematological characteristics","volume":"9","author":"M Matsumoto","year":"1979","journal-title":"Jpn J Clin Oncol"},{"issue":"12","key":"pone.0248001.ref020","doi-asserted-by":"crossref","first-page":"1068","DOI":"10.1016\/S1474-4422(06)70628-7","article-title":"The HTLV-1 neurological complex","volume":"5","author":"AQ Araujo","year":"2006","journal-title":"The Lancet Neurology"},{"issue":"5","key":"pone.0248001.ref021","first-page":"787","article-title":"HABA (HTLV-I associated bronchiolo-alveolar disorder)","volume":"30","author":"I Kimura","year":"1992","journal-title":"Nihon Kyobu Shikkan Gakkai Zasshi"},{"issue":"2","key":"pone.0248001.ref022","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S0002-9394(14)73974-1","article-title":"Uveitis associated with human T-cell lymphotropic virus type I","volume":"114","author":"M Mochizuki","year":"1992","journal-title":"American journal of ophthalmology"},{"issue":"11","key":"pone.0248001.ref023","first-page":"2300","article-title":"Higher prevalence of fibromyalgia in patients infected with human T cell lymphotropic virus type I","volume":"33","author":"BA Cruz","year":"2006","journal-title":"The Journal of rheumatology"},{"issue":"2","key":"pone.0248001.ref024","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1590\/S1807-59322007000200015","article-title":"Urinary and sexual manifestations of patients infected by HTLV-I","volume":"62","author":"P Oliveira","year":"2007","journal-title":"Clinics"},{"issue":"2","key":"pone.0248001.ref025","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1111\/j.1365-2249.2004.02524.x","article-title":"Interference with immune function by HTLV-1","volume":"137","author":"PK Goon","year":"2004","journal-title":"Clinical and experimental immunology"},{"issue":"9","key":"pone.0248001.ref026","doi-asserted-by":"crossref","first-page":"2037","DOI":"10.3390\/v2092037","article-title":"Human T lymphotropic virus type 1 (HTLV-1): molecular biology and oncogenesis","volume":"2","author":"P Kannian","year":"2010","journal-title":"Viruses"},{"key":"pone.0248001.ref027","doi-asserted-by":"crossref","first-page":"5682","DOI":"10.1128\/JVI.64.11.5682-5687.1990","article-title":"In vivo cellular tropism of human T-cell leukemia virus type 1","volume":"64","author":"JH Richardson","year":"1990","journal-title":"Journal of Virology"},{"key":"pone.0248001.ref028","doi-asserted-by":"crossref","first-page":"9922","DOI":"10.1128\/JVI.77.18.9922-9930.2003","article-title":"Human T-Cell Leukemia Virus Type 1 Envelope Glycoprotein gp46 Interacts with Cell Surface Heparan Sulfate Proteoglycans","volume":"77","author":"JD Pi\u00f1on","year":"2003","journal-title":"Journal of Virology"},{"key":"pone.0248001.ref029","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1016\/S0300-9084(01)01290-1","article-title":"Heparan sulfate: Anchor for viral intruders?","volume":"83","author":"D Spillmann","year":"2001","journal-title":"Biochimie"},{"key":"pone.0248001.ref030","doi-asserted-by":"crossref","first-page":"184","DOI":"10.1016\/j.virol.2006.01.045","article-title":"Infection of CD4+ T lymphocytes by the human T cell leukemia virus type 1 is mediated by the glucose transporter GLUT-1: Evidence using antibodies specific to the receptor\u2019s large extracellular domain","volume":"349","author":"Q Jin","year":"2006","journal-title":"Virology"},{"key":"pone.0248001.ref031","doi-asserted-by":"crossref","first-page":"6844","DOI":"10.1128\/JVI.02719-05","article-title":"Neuropilin-1 Is Involved in Human T-Cell Lymphotropic Virus Type 1 Entry","volume":"80","author":"D Ghez","year":"2006","journal-title":"Journal of Virology"},{"issue":"12","key":"pone.0248001.ref032","doi-asserted-by":"crossref","first-page":"3856","DOI":"10.1073\/pnas.81.12.3856","article-title":"Human T-cell leukemia virus-associated membrane antigens: identity of the major antigens recognized after virus infection","volume":"81","author":"TH Lee","year":"1984","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"pone.0248001.ref033","doi-asserted-by":"crossref","first-page":"3718","DOI":"10.1128\/JVI.62.10.3718-3728.1988","article-title":"Processing of gag precursor polyprotein of human T-cell leukemia virus type I by virus-encoded protease","volume":"62","author":"SH Nam","year":"1988","journal-title":"Journal of Virology"},{"key":"pone.0248001.ref034","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1006\/viro.1994.1131","article-title":"Structure and expression of the human T-cell leukemia virus type 1 envelope protein","volume":"199","author":"E Paine","year":"1994","journal-title":"Virology"},{"key":"pone.0248001.ref035","doi-asserted-by":"crossref","first-page":"4570","DOI":"10.1128\/JVI.66.7.4570-4575.1992","article-title":"Role of human T-cell leukemia virus type 1 X region proteins in immortalization of primary human lymphocytes in culture","volume":"66","author":"R Grassmann","year":"1992","journal-title":"Journal of Virology"},{"issue":"9","key":"pone.0248001.ref036","doi-asserted-by":"crossref","first-page":"3351","DOI":"10.1073\/pnas.86.9.3351","article-title":"Transformation to continuous growth of primary human T lymphocytes by human T-cell leukemia virus type I X-region genes transduced by a Herpesvirus saimiri vector","volume":"86","author":"R Grassmann","year":"1989","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"pone.0248001.ref037","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1126\/science.2888190","article-title":"The tat gene of human Lymphotropic virus type I induces mesenchymal tumors in transgenic mice","volume":"237","author":"M Nerenberg","year":"1987","journal-title":"Science"},{"issue":"3","key":"pone.0248001.ref038","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1073\/pnas.87.3.1071","article-title":"Oncogenic transformation by the tax gene of human T-cell leukemia virus type I in vitro","volume":"87","author":"A Tanaka","year":"1990","journal-title":"Proc. Natl. Acad. Sci. U. S. A"},{"key":"pone.0248001.ref039","first-page":"433","article-title":"Tax protein of human T-cell leukemia virus type I is required for maintenance of the transformed phenotype","volume":"7","author":"S Yamaoka","year":"1992","journal-title":"Oncogene"},{"key":"pone.0248001.ref040","doi-asserted-by":"crossref","first-page":"4856","DOI":"10.1128\/JVI.73.6.4856-4865.1999","article-title":"Immortalization of CD4+ and CD8+ T Lymphocytes by Human T-Cell Leukemia Virus Type 1 Tax Mutants Expressed in a Functional Molecular Clone","volume":"73","author":"MD Robek","year":"1999","journal-title":"Journal of Virology"},{"key":"pone.0248001.ref041","doi-asserted-by":"crossref","first-page":"5194","DOI":"10.1128\/JVI.70.8.5194-5202.1996","article-title":"The tax gene of human T-cell leukemia virus type 2 is essential for transformation of human T lymphocytes","volume":"70","author":"TM Ross","year":"1996","journal-title":"Journal of Virology"},{"issue":"3","key":"pone.0248001.ref042","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1128\/JVI.74.3.1094-1100.2000","article-title":"Functional role of pX open reading frame II of human T-lymphotropic virus type 1 in maintenance of viral loads in vivo","volume":"74","author":"JT Bartoe","year":"2000","journal-title":"Journal of virology"},{"key":"pone.0248001.ref043","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1006\/viro.1997.8781","article-title":"X-I and X-II open reading frames of HTLV-I are not required for virus replication or for immortalization of primary T-cells in vitro","volume":"237","author":"D Derse","year":"1997","journal-title":"Virology"},{"issue":"12","key":"pone.0248001.ref044","first-page":"4701","article-title":"Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo","volume":"91","author":"ND Collins","year":"1998","journal-title":"Blood, The Journal of the American Society of Hematology"},{"issue":"1","key":"pone.0248001.ref045","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1186\/1742-4690-3-15","article-title":"HTLV-I antisense transcripts initiating in the 3\u2019LTR are alternatively spliced and polyadenylated","volume":"3","author":"MH Cavanagh","year":"2006","journal-title":"Retrovirology"},{"issue":"11","key":"pone.0248001.ref046","first-page":"859","article-title":"AP-1: a double-edged sword in tumorigenesis. Nature reviews","volume":"3","author":"R Eferl","year":"2003","journal-title":"Cancer"},{"issue":"16","key":"pone.0248001.ref047","doi-asserted-by":"crossref","first-page":"2449","DOI":"10.1016\/j.ejca.2005.08.008","article-title":"The Fos family of transcription factors and their role in tumourigenesis","volume":"41","author":"K Milde-Langosch","year":"2005","journal-title":"European journal of cancer"},{"issue":"35","key":"pone.0248001.ref048","doi-asserted-by":"crossref","first-page":"4757","DOI":"10.1038\/onc.2008.120","article-title":"Multiple facets of junD gene expression are atypical among AP-1 family members","volume":"27","author":"JM Hernandez","year":"2008","journal-title":"Oncogene"},{"issue":"44","key":"pone.0248001.ref049","doi-asserted-by":"crossref","first-page":"43620","DOI":"10.1074\/jbc.M307275200","article-title":"The HBZ factor of human T-cell leukemia virus type I dimerizes with transcription factors JunB and c-Jun and modulates their transcriptional activity","volume":"278","author":"J Basbous","year":"2003","journal-title":"Journal of Biological Chemistry"},{"issue":"35","key":"pone.0248001.ref050","doi-asserted-by":"crossref","first-page":"23903","DOI":"10.1074\/jbc.M803116200","article-title":"An interaction between the human T cell leukemia virus type 1 basic leucine zipper factor (HBZ) and the KIX domain of p300\/CBP contributes to the down-regulation of tax-dependent viral transcription by HBZ","volume":"283","author":"I Clerc","year":"2008","journal-title":"Journal of Biological Chemistry"},{"issue":"1\u20133","key":"pone.0248001.ref051","doi-asserted-by":"crossref","first-page":"165","DOI":"10.1016\/S0014-5793(04)00225-X","article-title":"HBZ interacts with JunD and stimulates its transcriptional activity","volume":"562","author":"S Th\u00e9bault","year":"2004","journal-title":"FEBS letters"},{"issue":"4","key":"pone.0248001.ref052","doi-asserted-by":"crossref","first-page":"1543","DOI":"10.1128\/JVI.00480-06","article-title":"Human T-cell leukemia virus type 1 (HTLV-1) bZIP protein interacts with the cellular transcription factor CREB to inhibit HTLV-1 transcription","volume":"81","author":"I Lemasson","year":"2007","journal-title":"Journal of virology"},{"issue":"3","key":"pone.0248001.ref053","doi-asserted-by":"crossref","first-page":"720","DOI":"10.1073\/pnas.0507631103","article-title":"HTLV-I basic leucine zipper factor gene mRNA supports proliferation of adult T cell leukemia cells","volume":"103","author":"Y Satou","year":"2006","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"1","key":"pone.0248001.ref054","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1146\/annurev.immunol.19.1.475","article-title":"Multiple viral strategies of HTLV-1 for dysregulation of cell growth control","volume":"19","author":"M Yoshida","year":"2001","journal-title":"Annual review of immunology"},{"issue":"1","key":"pone.0248001.ref055","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1186\/1742-4690-5-76","article-title":"The HTLV-1 tax interactome","volume":"5","author":"M Boxus","year":"2008","journal-title":"Retrovirology"},{"issue":"4","key":"pone.0248001.ref056","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1002\/ijc.20007","article-title":"Genetic and epigenetic inactivation of tax gene in adult T-cell leukemia cells","volume":"109","author":"S Takeda","year":"2004","journal-title":"International journal of cancer"},{"issue":"8","key":"pone.0248001.ref057","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1093\/intimm\/3.8.761","article-title":"Predominant recognition of human T cell leukemia virus type I (HTLV-I) pX gene products by human CD8+ cytotoxic T cells directed against HTLV-I-infected cells","volume":"3","author":"M Kannagi","year":"1991","journal-title":"International immunology"},{"issue":"13","key":"pone.0248001.ref058","doi-asserted-by":"crossref","first-page":"4243","DOI":"10.1002\/j.1460-2075.1990.tb07872.x","article-title":"Mutations introduced along the HTLV-I envelope gene result in a non-functional protein: a basis for envelope conservation?","volume":"9","author":"C Pique","year":"1990","journal-title":"The EMBO Journal"},{"issue":"3","key":"pone.0248001.ref059","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1007\/BF00393183","article-title":"Intracellular processing and immunogenicity of the envelope proteins of human T-cell leukemia virus type I that are expressed from recombinant vaccinia viruses","volume":"3","author":"M Seki","year":"1990","journal-title":"Virus genes"},{"issue":"3","key":"pone.0248001.ref060","doi-asserted-by":"crossref","first-page":"1564","DOI":"10.1128\/JVI.70.3.1564-1569.1996","article-title":"Identification and mapping of functional domains on human T-cell lymphotropic virus type 1 envelope proteins by using synthetic peptides","volume":"70","author":"Y Sagara","year":"1996","journal-title":"Journal of virology"},{"issue":"9","key":"pone.0248001.ref061","doi-asserted-by":"crossref","first-page":"7609","DOI":"10.1128\/JVI.72.9.7609-7614.1998","article-title":"Analysis of functional conservation in the surface and transmembrane glycoprotein subunits of human T-cell leukemia virus type 1 (HTLV-1) and HTLV-2","volume":"72","author":"AR Rosenberg","year":"1998","journal-title":"Journal of virology"},{"issue":"75","key":"pone.0248001.ref062","first-page":"1","article-title":"Molecular characterization of HTLV-1 gp46 glycoprotein from health carriers and HAM\/TSP infected individuals","volume":"10","author":"ACAM Miranda","year":"2013","journal-title":"Virology Journal"},{"key":"pone.0248001.ref063","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1097\/00042560-199600001-00015","article-title":"The HTLV-I envelope glycoproteins: structure and functions","volume":"13","author":"L Delamarre","year":"1996","journal-title":"JAIDS Journal of Acquired Immune Deficiency Syndromes"},{"issue":"1","key":"pone.0248001.ref064","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/0304-3835(92)90274-Y","article-title":"Characterization of a B-cell immunodominant epitope of human T-lymphotropic virus type 1 (HTLV-I) envelope gp46","volume":"66","author":"MD Lairmore","year":"1992","journal-title":"Cancer letters"},{"issue":"3","key":"pone.0248001.ref065","doi-asserted-by":"crossref","first-page":"971","DOI":"10.4049\/jimmunol.142.3.971","article-title":"Mapping of immunogenic regions of human T cell leukemia virus type I (HTLV-I) gp46 and gp21 envelope glycoproteins with env-encoded synthetic peptides and a monoclonal antibody to gp46","volume":"142","author":"TJ Palker","year":"1989","journal-title":"The Journal of Immunology"},{"issue":"13","key":"pone.0248001.ref066","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.1073\/pnas.88.13.5754","article-title":"Identification of type-specific linear epitopes in the glycoproteins gp46 and gp21 of human T-cell leukemia viruses type I and type II using synthetic peptides","volume":"88","author":"P Horal","year":"1991","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"3","key":"pone.0248001.ref067","doi-asserted-by":"crossref","first-page":"1628","DOI":"10.1128\/JVI.65.3.1628-1633.1991","article-title":"Human T-cell leukemia-lymphoma virus type I (HTLV-I) expression in fresh peripheral blood mononuclear cells from patients with tropical spastic paraparesis\/HTLV-I-associated myelopathy","volume":"65","author":"ANTOINE Gessain","year":"1991","journal-title":"Journal of virology"},{"issue":"14","key":"pone.0248001.ref068","doi-asserted-by":"crossref","first-page":"5620","DOI":"10.1073\/pnas.86.14.5620","article-title":"Detection of mRNA for the tax1\/rex1 gene of human T-cell leukemia virus type I in fresh peripheral blood mononuclear cells of adult T-cell leukemia patients and viral carriers by using the polymerase chain reaction","volume":"86","author":"T Kinoshita","year":"1989","journal-title":"Proceedings of the National Academy of Sciences"},{"issue":"32","key":"pone.0248001.ref069","doi-asserted-by":"crossref","first-page":"22284","DOI":"10.1074\/jbc.M114.549659","article-title":"Human T-lymphotropic virus type 1-infected cells secrete exosomes that contain Tax protein","volume":"289","author":"E Jaworski","year":"2014","journal-title":"J Biol Chem"},{"key":"pone.0248001.ref070","doi-asserted-by":"crossref","first-page":"571","DOI":"10.1385\/1-59259-890-0:571","volume-title":"InThe proteomics protocols handbook","author":"E Gasteiger","year":"2005"},{"issue":"6","key":"pone.0248001.ref071","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1093\/bioinformatics\/11.6.681","article-title":"SOPMA: significant improvements in protein secondary structure prediction by consensus prediction from multiple alignments","volume":"11","author":"C Geourjon","year":"1995","journal-title":"Bioinformatics"},{"issue":"4","key":"pone.0248001.ref072","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1093\/bioinformatics\/16.4.404","article-title":"The PSIPRED protein structure prediction server","volume":"16","author":"LJ McGuffin","year":"2000","journal-title":"Bioinformatics"},{"issue":"6","key":"pone.0248001.ref073","doi-asserted-by":"crossref","first-page":"845","DOI":"10.1038\/nprot.2015.053","article-title":"The Phyre2 web portal for protein modeling, prediction and analysis","volume":"10","author":"LA Kelley","year":"2015","journal-title":"Nature protocols"},{"key":"pone.0248001.ref074","doi-asserted-by":"crossref","first-page":"152","DOI":"10.1093\/nar\/gkl187","article-title":"(PS)2: protein structure prediction server","volume":"34","author":"CC Chen","year":"2006","journal-title":"Nucleic Acids Res"},{"issue":"1","key":"pone.0248001.ref075","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1186\/1471-2105-10-366","article-title":"(PS)2-v2: template-based protein structure prediction server","volume":"10","author":"CC Chen","year":"2009","journal-title":"Bmc Bioinformatics"},{"issue":"7","key":"pone.0248001.ref076","doi-asserted-by":"crossref","first-page":"951","DOI":"10.1093\/bioinformatics\/bti125","article-title":"Protein homology detection by HMM\u2013HMM comparison","volume":"21","author":"J S\u00f6ding","year":"2005","journal-title":"Bioinformatics"},{"issue":"5","key":"pone.0248001.ref077","doi-asserted-by":"crossref","first-page":"1329","DOI":"10.1016\/j.jmb.2010.01.074","article-title":"Protein folding requires crowd control in a simulated cell","volume":"397","author":"BR Jefferys","year":"2010","journal-title":"Journal of molecular biology"},{"issue":"10","key":"pone.0248001.ref078","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1016\/j.bpj.2011.10.024","article-title":"Improving the physical realism and structural accuracy of protein models by a two-step atomic-level energy minimization","volume":"101","author":"D Xu","year":"2011","journal-title":"Biophysical journal"},{"issue":"W1","key":"pone.0248001.ref079","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1093\/nar\/gkw336","article-title":"3Drefine: an interactive web server for efficient protein structure refinement","volume":"44","author":"D Bhattacharya","year":"2016","journal-title":"Nucleic acids research"},{"issue":"4","key":"pone.0248001.ref080","doi-asserted-by":"crossref","first-page":"1049","DOI":"10.1006\/jmbi.1993.1351","article-title":"Main-chain bond lengths and bond angles in protein structures","volume":"231","author":"RA Laskowski","year":"1993","journal-title":"Journal of molecular biology"},{"issue":"9","key":"pone.0248001.ref081","doi-asserted-by":"crossref","first-page":"1511","DOI":"10.1002\/pro.5560020916","article-title":"Verification of protein structures: patterns of nonbonded atomic interactions","volume":"2","author":"C Colovos","year":"1993","journal-title":"Protein science"},{"key":"pone.0248001.ref082","first-page":"396","volume-title":"InMethods in enzymology","author":"D Eisenberg","year":"1997"},{"issue":"W1","key":"pone.0248001.ref083","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1093\/nar\/gkx346","article-title":"BepiPred-2.0: improving sequence-based B-cell epitope prediction using conformational epitopes","volume":"45","author":"MC Jespersen","year":"2017","journal-title":"Nucleic acids research"},{"issue":"3","key":"pone.0248001.ref084","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1006\/jmbi.2000.4315","article-title":"Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes","volume":"305","author":"A Krogh","year":"2001","journal-title":"Journal of molecular biology"},{"issue":"1","key":"pone.0248001.ref085","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/1471-2105-8-4","article-title":"VaxiJen: a server for prediction of protective antigens, tumour antigens and subunit vaccines","volume":"8","author":"IA Doytchinova","year":"2007","journal-title":"BMC bioinformatics"},{"issue":"6","key":"pone.0248001.ref086","doi-asserted-by":"crossref","first-page":"2278","DOI":"10.1007\/s00894-014-2278-5","article-title":"AllerTOP v. 2\u2014a server for in silico prediction of allergens","volume":"20","author":"I Dimitrov","year":"2014","journal-title":"Journal of molecular modeling"},{"issue":"9","key":"pone.0248001.ref087","doi-asserted-by":"crossref","first-page":"73957","DOI":"10.1371\/journal.pone.0073957","article-title":"Open Source Drug Discovery Consortium. In silico approach for predicting toxicity of peptides and proteins","volume":"8","author":"S Gupta","year":"2013","journal-title":"PloS one"},{"issue":"1","key":"pone.0248001.ref088","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1186\/1471-2105-8-424","article-title":"Large-scale validation of methods for cytotoxic T-lymphocyte epitope prediction","volume":"8","author":"MV Larsen","year":"2007","journal-title":"BMC bioinformatics"},{"issue":"5","key":"pone.0248001.ref089","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1034\/j.1399-0039.2003.00112.x","article-title":"Sensitive quantitative predictions of peptide-MHC binding by a \u2018Query by Committee\u2019artificial neural network approach","volume":"62","author":"S Buus","year":"2003","journal-title":"Tissue antigens"},{"issue":"1","key":"pone.0248001.ref090","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1186\/1471-2105-6-132","article-title":"Generating quantitative models describing the sequence specificity of biological processes with the stabilized matrix method","volume":"6","author":"B Peters","year":"2005","journal-title":"BMC bioinformatics"},{"issue":"1","key":"pone.0248001.ref091","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-7-1","article-title":"Predicting population coverage of T-cell epitope-based diagnostics and vaccines","volume":"7","author":"HH Bui","year":"2006","journal-title":"BMC bioinformatics"},{"issue":"10","key":"pone.0248001.ref092","doi-asserted-by":"crossref","first-page":"e1003266","DOI":"10.1371\/journal.pcbi.1003266","article-title":"Properties of MHC class I presented peptides that enhance immunogenicity","volume":"9","author":"JJ Calis","year":"2013","journal-title":"PLoS Comput Biol"},{"issue":"2","key":"pone.0248001.ref093","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/jcc.21334","article-title":"AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading","volume":"31","author":"O Trott","year":"2010","journal-title":"Journal of computational chemistry"},{"issue":"1","key":"pone.0248001.ref094","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1093\/nar\/28.1.10","article-title":"Database resources of the national center for biotechnology information","volume":"28","author":"DL Wheeler","year":"2000","journal-title":"Nucleic acids research"},{"issue":"suppl_2","key":"pone.0248001.ref095","doi-asserted-by":"crossref","first-page":"498","DOI":"10.1093\/nar\/gkp323","article-title":"PEP-FOLD: an online resource for de novo peptide structure prediction","volume":"37","author":"J Maupetit","year":"2009","journal-title":"Nucleic acids research"},{"issue":"10","key":"pone.0248001.ref096","doi-asserted-by":"crossref","first-page":"1357","DOI":"10.1016\/j.addr.2012.09.039","article-title":"Fusion protein linkers: property, design and functionality","volume":"65","author":"X Chen","year":"2013","journal-title":"Advanced drug delivery reviews"},{"issue":"1","key":"pone.0248001.ref097","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1186\/s12967-018-1560-1","article-title":"Computer-aided prediction of antigen presenting cell modulators for designing peptide-based vaccine adjuvants","volume":"16","author":"G Nagpal","year":"2018","journal-title":"Journal of translational medicine"},{"issue":"4","key":"pone.0248001.ref098","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1038\/nprot.2010.5","article-title":"I-TASSER: a unified platform for automated protein structure and function prediction","volume":"5","author":"A Roy","year":"2010","journal-title":"Nature protocols"},{"issue":"1","key":"pone.0248001.ref099","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1038\/nmeth.3213","article-title":"The I-TASSER Suite: protein structure and function prediction","volume":"12","author":"J Yang","year":"2015","journal-title":"Nature methods"},{"issue":"W1","key":"pone.0248001.ref100","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1093\/nar\/gkv342","article-title":"I-TASSER server: new development for protein structure and function predictions","volume":"43","author":"J Yang","year":"2015","journal-title":"Nucleic acids research"},{"issue":"3","key":"pone.0248001.ref101","doi-asserted-by":"crossref","first-page":"444","DOI":"10.1093\/bioinformatics\/btw638","article-title":"PyMod 2.0: improvements in protein sequence-structure analysis and homology modeling within PyMOL","volume":"33","author":"G Janson","year":"2017","journal-title":"Bioinformatics"},{"issue":"1","key":"pone.0248001.ref102","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1471-2105-14-346","article-title":"Disulfide by Design 2.0: a web-based tool for disulfide engineering in proteins","volume":"14","author":"DB Craig","year":"2013","journal-title":"BMC bioinformatics"},{"issue":"suppl_2","key":"pone.0248001.ref103","doi-asserted-by":"crossref","first-page":"526","DOI":"10.1093\/nar\/gki376","article-title":"JCat: a novel tool to adapt codon usage of a target gene to its potential expression host","volume":"33","author":"A Grote","year":"2005","journal-title":"Nucleic acids research"},{"issue":"11","key":"pone.0248001.ref104","doi-asserted-by":"crossref","first-page":"2924","DOI":"10.1016\/j.celrep.2018.02.067","article-title":"Gasdermin D exerts anti-inflammatory effects by promoting neutrophil death","volume":"22","author":"H Kambara","year":"2018","journal-title":"Cell reports"},{"issue":"3","key":"pone.0248001.ref105","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1007\/s10529-014-1731-y","article-title":"Rapid detection of 6\u00d7-histidine-labeled recombinant proteins by immunochromatography using dye-labeled cellulose nanobeads","volume":"37","author":"ES Choi","year":"2015","journal-title":"Biotechnology letters"},{"key":"pone.0248001.ref106","doi-asserted-by":"crossref","first-page":"316","DOI":"10.3389\/fimmu.2014.00316","article-title":"A comparative review of toll-like receptor 4 expression and functionality in different animal species","volume":"5","author":"C Vaure","year":"2014","journal-title":"Frontiers in immunology"},{"key":"pone.0248001.ref107","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1007\/3-540-45784-4_14","volume-title":"InInternational workshop on algorithms in bioinformatics","author":"D Duhovny","year":"2002"},{"issue":"suppl_2","key":"pone.0248001.ref108","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1093\/nar\/gki481","article-title":"PatchDock and SymmDock: servers for rigid and symmetric docking","volume":"33","author":"D Schneidman-Duhovny","year":"2005","journal-title":"Nucleic acids research"},{"issue":"1","key":"pone.0248001.ref109","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s12977-019-0484-z","article-title":"Impact of host immunity on HTLV-1 pathogenesis: potential of Tax-targeted immunotherapy against ATL","volume":"16","author":"M Kannagi","year":"2019","journal-title":"Retrovirology"},{"key":"pone.0248001.ref110","doi-asserted-by":"crossref","first-page":"2563","DOI":"10.3389\/fmicb.2017.02563","article-title":"Role of HTLV-1 Tax and HBZ in the pathogenesis of HAM\/TSP","volume":"8","author":"Y Enose-Akahata","year":"2017","journal-title":"Frontiers in microbiology"},{"issue":"8","key":"pone.0248001.ref111","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1099\/vir.0.010199-0","article-title":"HBZ is an immunogenic protein, but not a target antigen for human T-cell leukemia virus type 1-specific cytotoxic T lymphocytes","volume":"90","author":"K Suemori","year":"2009","journal-title":"Journal of General Virology"},{"key":"pone.0248001.ref112","doi-asserted-by":"crossref","first-page":"382","DOI":"10.1016\/j.bj.2016.11.004","article-title":"In silico structure analysis and epitope prediction of E3 CR1-beta protein of Human Adenovirus E for vaccine design","volume":"39","author":"NIA Patwary","year":"2016","journal-title":"Biomedical Journal"},{"key":"pone.0248001.ref113","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/978-3-030-32459-9_3","volume-title":"InHIV\/AIDS: Immunochemistry, Reductionism and Vaccine Design","author":"MH Van Regenmortel","year":"2019"},{"key":"pone.0248001.ref114","doi-asserted-by":"crossref","first-page":"826","DOI":"10.3389\/fimmu.2018.00826","article-title":"Epitope discovery and Synthetic Vaccine design","volume":"9","author":"CB Palatnik-de-Sousa","year":"2018","journal-title":"Frontiers in immunology"},{"key":"pone.0248001.ref115","doi-asserted-by":"crossref","first-page":"819","DOI":"10.3389\/fmicb.2019.00819","article-title":"HTLV-1 HBZ protein resides exclusively in the cytoplasm of infected cells in asymptomatic carriers and HAM\/TSP patients","volume":"10","author":"G Forlani","year":"2019","journal-title":"Frontiers in Microbiology"},{"key":"pone.0248001.ref116","doi-asserted-by":"crossref","first-page":"182","DOI":"10.3389\/fimmu.2014.00182","article-title":"Understanding MHC class I presentation of viral antigens by human dendritic cells as a basis for rational design of therapeutic vaccines","volume":"5","author":"N Van Montfoort","year":"2014","journal-title":"Frontiers in immunology"},{"key":"pone.0248001.ref117","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.meegid.2017.10.022","article-title":"Overlapping CD8+ and CD4+ T-cell epitopes identification for the progression of epitope-based peptide vaccine from nucleocapsid and glycoprotein of emerging Rift Valley fever virus using immunoinformatics approach","volume":"56","author":"UK Adhikari","year":"2017","journal-title":"Infection, Genetics and Evolution"},{"key":"pone.0248001.ref118","doi-asserted-by":"crossref","first-page":"246","DOI":"10.3389\/fchem.2018.00246","article-title":"An immunopharmacoinformatics approach in development of vaccine and drug candidates for West Nile virus","volume":"6","author":"MU Hossain","year":"2018","journal-title":"Frontiers in Chemistry"},{"key":"pone.0248001.ref119","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":"A Gessain","year":"2012","journal-title":"Frontiers in microbiology"},{"issue":"1","key":"pone.0248001.ref120","first-page":"1","article-title":"In-silico design of a multi-epitope vaccine candidate against onchocerciasis and related filarial diseases","volume":"9","author":"RA Shey","year":"2019","journal-title":"Scientific reports"},{"issue":"1","key":"pone.0248001.ref121","first-page":"1","article-title":"Exploring dengue genome to construct a multi-epitope based subunit vaccine by utilizing immunoinformatics approach to battle against dengue infection","volume":"7","author":"M Ali","year":"2017","journal-title":"Scientific reports"},{"issue":"1","key":"pone.0248001.ref122","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-08842-w","article-title":"Exploring Leishmania secretory proteins to design B and T cell multi-epitope subunit vaccine using immunoinformatics approach","volume":"7","author":"N Khatoon","year":"2017","journal-title":"Scientific reports"},{"issue":"2","key":"pone.0248001.ref123","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1093\/protein\/4.2.155","article-title":"Correlation between stability of a protein and its dipeptide composition: a novel approach for predicting in vivo stability of a protein from its primary sequence","volume":"4","author":"K Guruprasad","year":"1990","journal-title":"Protein Engineering, Design and Selection"},{"issue":"1","key":"pone.0248001.ref124","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1110\/ps.26801","article-title":"Disulfide bond effects on protein stability: Designed variants of Cucurbita maxima trypsin inhibitor-V","volume":"10","author":"M Zavodszky","year":"2001","journal-title":"Protein Science"},{"issue":"9","key":"pone.0248001.ref125","doi-asserted-by":"crossref","first-page":"4880","DOI":"10.1128\/JVI.02493-14","article-title":"Oncogenic human T-cell lymphotropic virus type 1 tax suppression of primary innate immune signaling pathways","volume":"89","author":"J Hyun","year":"2015","journal-title":"Journal of virology"},{"key":"pone.0248001.ref126","doi-asserted-by":"crossref","DOI":"10.1155\/2010\/184328","article-title":"The battle between virus and host: modulation of Toll-like receptor signaling pathways by virus infection","volume":"2010","author":"SI Yokota","year":"2010","journal-title":"Mediators of 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