{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T16:59:14Z","timestamp":1787763554310,"version":"build-2784847793"},"reference-count":101,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2024,11,9]],"date-time":"2024-11-09T00:00:00Z","timestamp":1731110400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["AI166097"],"award-info":[{"award-number":["AI166097"]}]},{"name":"NIH","award":["GR18257"],"award-info":[{"award-number":["GR18257"]}]},{"name":"NIH","award":["GR17982"],"award-info":[{"award-number":["GR17982"]}]},{"name":"KUMC School of Medicine","award":["AI166097"],"award-info":[{"award-number":["AI166097"]}]},{"name":"KUMC School of Medicine","award":["GR18257"],"award-info":[{"award-number":["GR18257"]}]},{"name":"KUMC School of Medicine","award":["GR17982"],"award-info":[{"award-number":["GR17982"]}]},{"name":"KUMC Pathology Pilot","award":["AI166097"],"award-info":[{"award-number":["AI166097"]}]},{"name":"KUMC Pathology Pilot","award":["GR18257"],"award-info":[{"award-number":["GR18257"]}]},{"name":"KUMC Pathology Pilot","award":["GR17982"],"award-info":[{"award-number":["GR17982"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Human T-cell leukemia virus (HTLV-1) is the etiological agent of lymphoproliferative diseases such as adult T-cell leukemia and T-cell lymphoma (ATL) and a neurodegenerative disease known as HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP). While several molecular clones of HTLV-1 have been published, all were isolated from samples derived from patients with adult T-cell leukemia. Here, we report the characterization of an HTLV-1 infectious molecular clone isolated from a sample of a patient with HAM\/TSP disease. Genetic comparative analyses of the HAM\/TSP molecular clone (pBST) revealed unique genetic alterations and specific viral mRNA expression patterns. Interestingly, our clone also harbors characteristics previously published to favor the development of HAM\/TSP disease. The molecular clone is capable of infection and immortalization of human primary T cells in vitro. Our studies further demonstrate that the HTLV-1 virus produced from primary T cells transfected with pBST or ACH molecular clones cannot sustain long-term expansion, and cells cease to proliferate after 3\u20134 months in culture. In contrast, long-term proliferation and immortalization were achieved if the virus was transmitted from dendritic cells to primary T cells, and secondary infection of 729B cells in vitro was demonstrated. In both primary T cells and 729B cells, pBST and ACH were latent, and only hbz viral RNA was detected. This study suggests that HTLV-1 transmission from DC to T cells favors the immortalization of latently infected cells.<\/jats:p>","DOI":"10.3390\/v16111755","type":"journal-article","created":{"date-parts":[[2024,11,11]],"date-time":"2024-11-11T03:52:07Z","timestamp":1731297127000},"page":"1755","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Characterization of HTLV-1 Infectious Molecular Clone Isolated from Patient with HAM\/TSP and Immortalization of Human Primary T-Cell Lines"],"prefix":"10.3390","volume":"16","author":[{"given":"Marcia","family":"Bellon","sequence":"first","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8057-7835","authenticated-orcid":false,"given":"Pooja","family":"Jain","sequence":"additional","affiliation":[{"name":"Department of Microbiology & Immunology, Drexel University College of Medicine, Philadelphia, PA 19129, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5927-2869","authenticated-orcid":false,"given":"Christophe","family":"Nicot","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, 3901 Rainbow Blvd, Kansas City, KS 66160, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,11,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1146\/annurev.immunol.15.1.15","article-title":"Human T cell leukemia virus type I (HTLV-I) and human diseases","volume":"15","author":"Uchiyama","year":"1997","journal-title":"Annu. Rev. Immunol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"7415","DOI":"10.1073\/pnas.77.12.7415","article-title":"Detection and isolation of type C retrovirus particles from fresh and cultured lymphocytes of a patient with cutaneous T-cell lymphoma","volume":"77","author":"Poiesz","year":"1980","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"2031","DOI":"10.1073\/pnas.79.6.2031","article-title":"Isolation and characterization of retrovirus from cell lines of human adult T-cell leukemia and its implication in the disease","volume":"79","author":"Yoshida","year":"1982","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1016\/S0140-6736(85)92734-5","article-title":"Antibodies to human T-lymphotropic virus type-I in patients with tropical spastic paraparesis","volume":"2","author":"Gessain","year":"1985","journal-title":"Lancet"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1002\/ana.410210203","article-title":"Chronic progressive myelopathy associated with elevated antibodies to human T-lymphotropic virus type I and adult T-cell leukemialike cells","volume":"21","author":"Osame","year":"1987","journal-title":"Ann. Neurol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"581","DOI":"10.1136\/jcp.53.8.581","article-title":"HTLV-1 infections","volume":"53","author":"Bangham","year":"2000","journal-title":"J. Clin. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Legrand, N., McGregor, S., Bull, R., Bajis, S., Valencia, B.M., Ronnachit, A., Einsiedel, L., Gessain, A., Kaldor, J., and Martinello, M. (2022). Clinical and Public Health Implications of Human T-Lymphotropic Virus Type 1 Infection. Clin. Microbiol. Rev., 35.","DOI":"10.1128\/cmr.00078-21"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Iwanaga, M. (2020). Epidemiology of HTLV-1 Infection and ATL in Japan: An Update. Front. Microbiol., 11.","DOI":"10.3389\/fmicb.2020.01124"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1186\/s12977-019-0504-z","article-title":"Molecular epidemiology, genetic variability and evolution of HTLV-1 with special emphasis on African genotypes","volume":"16","author":"Afonso","year":"2019","journal-title":"Retrovirology"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3201\/eid0102.950201","article-title":"Travel and the emergence of infectious diseases","volume":"1","author":"Wilson","year":"1995","journal-title":"Emerg. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"taz007","DOI":"10.1093\/jtm\/taz007","article-title":"Infectious diseases at different stages of migration: An expert review","volume":"26","author":"Greenaway","year":"2019","journal-title":"J. Travel. Med."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1186\/s40249-024-01205-4","article-title":"Geography and health: Role of human translocation and access to care","volume":"13","author":"Brattig","year":"2024","journal-title":"Infect. Dis. Poverty"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1038\/s41579-021-00639-z","article-title":"Infectious disease in an era of global change","volume":"20","author":"Baker","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Miura, M., Naito, T., and Saito, M. (2022). Current Perspectives in Human T-Cell Leukemia Virus Type 1 Infection and Its Associated Diseases. Front. Med., 9.","DOI":"10.3389\/fmed.2022.867478"},{"key":"ref_15","first-page":"2299","article-title":"HTLV-1 persistence and the oncogenesis of adult T-cell leukemia\/lymphoma","volume":"141","author":"Bangham","year":"2023","journal-title":"Blood"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.1111\/bjh.15234","article-title":"Can we reduce the incidence of adult T-cell leukaemia\/lymphoma? Cost-effectiveness of human T-lymphotropic virus type 1 (HTLV-1) antenatal screening in the United Kingdom","volume":"184","author":"Malik","year":"2019","journal-title":"Br. J. Haematol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1089\/aid.2012.0132","article-title":"Human T cell lymphotropic virus type 1 viral load variability and long-term trends in asymptomatic carriers and in patients with human T cell lymphotropic virus type 1-related diseases","volume":"29","author":"Demontis","year":"2013","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/S0092-8674(03)00881-X","article-title":"The ubiquitous glucose transporter GLUT-1 is a receptor for HTLV","volume":"115","author":"Manel","year":"2003","journal-title":"Cell"},{"key":"ref_19","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":"Ghez","year":"2006","journal-title":"J. Virol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/cncr.10480","article-title":"Adult T-cell leukemia\/lymphoma: A cytopathologic, immunocytochemical, and flow cytometric study","volume":"96","author":"Dahmoush","year":"2002","journal-title":"Cancer"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1172\/JCI27198","article-title":"HTLV-1 propels untransformed CD4 lymphocytes into the cell cycle while protecting CD8 cells from death","volume":"116","author":"Sibon","year":"2006","journal-title":"J. Clin. Investig."},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Currer, R., Van Duyne, R., Jaworski, E., Guendel, I., Sampey, G., Das, R., Narayanan, A., and Kashanchi, F. (2012). HTLV tax: A fascinating multifunctional co-regulator of viral and cellular pathways. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00406"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"e02171-19","DOI":"10.1128\/JVI.02171-19","article-title":"Human T-Cell Lymphotropic Virus Type 1 Transactivator Tax Exploits the XPB Subunit of TFIIH during Viral Transcription","volume":"94","author":"Martella","year":"2020","journal-title":"J. Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"2441","DOI":"10.1182\/blood-2009-08-241117","article-title":"HTLV-I Tax-dependent and -independent events associated with immortalization of human primary T lymphocytes","volume":"115","author":"Bellon","year":"2010","journal-title":"Blood"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Baydoun, H.H., Bai, X.T., Shelton, S., and Nicot, C. (2012). HTLV-I tax increases genetic instability by inducing DNA double strand breaks during DNA replication and switching repair to NHEJ. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0042226"},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Nicot, C. (2015). HTLV-I Tax-Mediated Inactivation of Cell Cycle Checkpoints and DNA Repair Pathways Contribute to Cellular Transformation: \u201cA Random Mutagenesis Model\u201d. J. Cancer Sci., 2.","DOI":"10.13188\/2377-9292.1000009"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2523","DOI":"10.1182\/blood-2003-12-4251","article-title":"Transcriptional activation of hTERT through the NF-kappaB pathway in HTLV-I-transformed cells","volume":"104","author":"Horikawa","year":"2004","journal-title":"Blood"},{"key":"ref_28","first-page":"233","article-title":"Regulation of NF-kappaB by the HTLV-1 Tax protein","volume":"7","author":"Li","year":"1999","journal-title":"Gene Expr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E1269","DOI":"10.1073\/pnas.1715724115","article-title":"Sporadic on\/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells","volume":"115","author":"Mahgoub","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1095","DOI":"10.1182\/blood-2015-04-641118","article-title":"Protective effect of cytotoxic T lymphocytes targeting HTLV-1 bZIP factor","volume":"126","author":"Sugata","year":"2015","journal-title":"Blood"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1038\/s41408-023-00841-7","article-title":"Primary cells from patients with adult T cell leukemia\/lymphoma depend on HTLV-1 Tax expression for NF-kappaB activation and survival","volume":"13","author":"Hleihel","year":"2023","journal-title":"Blood Cancer J."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Alvarez, C., Gotuzzo, E., Vandamme, A.M., and Verdonck, K. (2016). Family Aggregation of Human T-Lymphotropic Virus 1-Associated Diseases: A Systematic Review. Front. Microbiol., 7.","DOI":"10.3389\/fmicb.2016.01674"},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Rosadas, C., and Taylor, G.P. (2019). Mother-to-Child HTLV-1 Transmission: Unmet Research Needs. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00999"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1186\/s12943-021-01370-2","article-title":"Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases","volume":"20","author":"Bellon","year":"2021","journal-title":"Mol. Cancer"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2023","DOI":"10.1182\/blood.2019002665","article-title":"Evolution of retrovirus-infected premalignant T-cell clones prior to Adult T-cell leukemia\/lymphoma diagnosis","volume":"135","author":"Rowan","year":"2020","journal-title":"Blood"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Saito, M. (2019). Association Between HTLV-1 Genotypes and Risk of HAM\/TSP. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01101"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"586","DOI":"10.3109\/13550289809114225","article-title":"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","volume":"4","author":"Nagai","year":"1998","journal-title":"J. Neurovirol."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Forlani, G., Baratella, M., Tedeschi, A., Pique, C., Jacobson, S., and Accolla, R.S. (2019). HTLV-1 HBZ Protein Resides Exclusively in the Cytoplasm of Infected Cells in Asymptomatic Carriers and HAM\/TSP Patients. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.00819"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"6460","DOI":"10.1128\/JVI.73.8.6460-6467.1999","article-title":"A lysine-to-arginine change found in natural alleles of the human T-cell lymphotropic\/leukemia virus type 1 p12(I) protein greatly influences its stability","volume":"73","author":"Trovato","year":"1999","journal-title":"J. Virol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1016\/0168-1702(93)90099-9","article-title":"Establishment of HTLV-I-infected cell lines from French, Guianese and West Indian patients and isolation of a proviral clone producing viral particles","volume":"30","author":"Nicot","year":"1993","journal-title":"Virus Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1093\/cvr\/cvaa066","article-title":"Pim1 maintains telomere length in mouse cardiomyocytes by inhibiting TGFbeta signalling","volume":"117","author":"Ebeid","year":"2021","journal-title":"Cardiovasc. Res."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/0166-0934(94)00097-Z","article-title":"Identification of HTLV-I- or HTLV-II-producing cells by cocultivation with BHK-21 cells stably transfected with a LTR-lacZ gene construct","volume":"51","author":"Portail","year":"1995","journal-title":"J. Virol. Methods"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1093\/molbev\/msp259","article-title":"SeaView Version 4: A Multiplatform Graphical User Interface for Sequence Alignment and Phylogenetic Tree Building","volume":"27","author":"Gouy","year":"2010","journal-title":"Mol. Biol. Evol."},{"key":"ref_44","first-page":"409","article-title":"Growth and manipulation of a human T-cell leukemia virus type 2 full-length molecular clone","volume":"304","author":"Anderson","year":"2005","journal-title":"Methods Mol. Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"6747","DOI":"10.1128\/JVI.00247-08","article-title":"Construction and characterization of a human T-cell lymphotropic virus type 3 infectious molecular clone","volume":"82","author":"Chevalier","year":"2008","journal-title":"J. Virol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1006\/viro.1994.1581","article-title":"Construction and characterization of infectious human T-cell leukemia virus type 1 molecular clones","volume":"204","author":"Kimata","year":"1994","journal-title":"Virology"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1907","DOI":"10.1128\/jvi.69.3.1907-1912.1995","article-title":"Virions released from cells transfected with a molecular clone of human T-cell leukemia virus type I give rise to primary and secondary infections of T cells","volume":"69","author":"Derse","year":"1995","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"6653","DOI":"10.1073\/pnas.93.13.6653","article-title":"Infectivity of chimeric human T-cell leukemia virus type I molecular clones assessed by naked DNA inoculation","volume":"93","author":"Zhao","year":"1996","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1089\/aid.1991.7.923","article-title":"Nucleotide sequence analysis of isolates of human T-lymphotropic virus type 1 of diverse geographical origins","volume":"7","author":"Ratner","year":"1991","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"2024","DOI":"10.1128\/jvi.69.4.2024-2030.1995","article-title":"Characterization of an infectious molecular clone of human T-cell leukemia virus type I","volume":"69","author":"Zhao","year":"1995","journal-title":"J. Virol."},{"key":"ref_51","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":"Derse","year":"1997","journal-title":"Virology"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.virol.2005.05.015","article-title":"Activation of human T cell leukemia virus type 1 LTR promoter and cellular promoter elements by T cell receptor signaling and HTLV-1 Tax expression","volume":"339","author":"Lin","year":"2005","journal-title":"Virology"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"6735","DOI":"10.1128\/JVI.78.13.6735-6743.2004","article-title":"Tax relieves transcriptional repression by promoting histone deacetylase 1 release from the human T-cell leukemia virus type 1 long terminal repeat","volume":"78","author":"Lu","year":"2004","journal-title":"J. Virol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3113","DOI":"10.1182\/blood-2010-10-312926","article-title":"The host genomic environment of the provirus determines the abundance of HTLV-1-infected T-cell clones","volume":"117","author":"Gillet","year":"2011","journal-title":"Blood"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Nakano, K., and Watanabe, T. (2012). HTLV-1 Rex: The courier of viral messages making use of the host vehicle. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00330"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1395","DOI":"10.3390\/v3081395","article-title":"Converging strategies in expression of human complex retroviruses","volume":"3","author":"Cavallari","year":"2011","journal-title":"Viruses"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1486","DOI":"10.1128\/JVI.02298-15","article-title":"Expression of Alternatively Spliced Human T-Cell Leukemia Virus Type 1 mRNAs Is Influenced by Mitosis and by a Novel cis-Acting Regulatory Sequence","volume":"90","author":"Cavallari","year":"2016","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1038\/nm984","article-title":"HTLV-1-encoded p30II is a post-transcriptional negative regulator of viral replication","volume":"10","author":"Nicot","year":"2004","journal-title":"Nat. Med."},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Fauquenoy, S., Robette, G., Kula, A., Vanhulle, C., Bouchat, S., Delacourt, N., Rodari, A., Marban, C., Schwartz, C., and Burny, A. (2017). Repression of Human T-lymphotropic virus type 1 Long Terminal Repeat sense transcription by Sp1 recruitment to novel Sp1 binding sites. Sci. Rep., 7.","DOI":"10.1038\/srep43221"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"9359","DOI":"10.1128\/JVI.00242-08","article-title":"Transcriptional control of spliced and unspliced human T-cell leukemia virus type 1 bZIP factor (HBZ) gene","volume":"82","author":"Yoshida","year":"2008","journal-title":"J. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3809","DOI":"10.1182\/blood-2010-05-284141","article-title":"Requirement of the human T-cell leukemia virus p12 and p30 products for infectivity of human dendritic cells and macaques but not rabbits","volume":"116","author":"Valeri","year":"2010","journal-title":"Blood"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2020","DOI":"10.1128\/JCM.42.5.2020-2026.2004","article-title":"High seroprevalence of human T-cell lymphotropic virus type 1 in blood donors in Guyana and molecular and phylogenetic analysis of new strains in the Guyana shelf (Guyana, Suriname, and French Guiana)","volume":"42","author":"Pouliquen","year":"2004","journal-title":"J. Clin. Microbiol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"3618","DOI":"10.1073\/pnas.80.12.3618","article-title":"Human adult T-cell leukemia virus: Complete nucleotide sequence of the provirus genome integrated in leukemia cell DNA","volume":"80","author":"Seiki","year":"1983","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Hanson, H.M., Willkomm, N.A., Yang, H., and Mansky, L.M. (2022). Human Retrovirus Genomic RNA Packaging. Viruses, 14.","DOI":"10.3390\/v14051094"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"905","DOI":"10.1128\/JVI.76.2.905-911.2002","article-title":"Intracellular distribution of human T-cell leukemia virus type 1 Gag proteins is independent of interaction with intracellular membranes","volume":"76","author":"Blot","year":"2002","journal-title":"J. Virol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3195","DOI":"10.1073\/pnas.88.8.3195","article-title":"Effect of mutations affecting the p6 gag protein on human immunodeficiency virus particle release","volume":"88","author":"Gottlinger","year":"1991","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"12164","DOI":"10.1128\/JVI.01158-08","article-title":"Human T-cell lymphotropic virus type 1 nucleocapsid protein-induced structural changes in transactivation response DNA hairpin measured by single-molecule fluorescence resonance energy transfer","volume":"82","author":"Darugar","year":"2008","journal-title":"J. Virol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"7278","DOI":"10.1128\/JVI.02239-09","article-title":"APOBEC3G generates nonsense mutations in human T-cell leukemia virus type 1 proviral genomes in vivo","volume":"84","author":"Fan","year":"2010","journal-title":"J. Virol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2489","DOI":"10.1099\/vir.0.80973-0","article-title":"Extensive editing of a small fraction of human T-cell leukemia virus type 1 genomes by four APOBEC3 cytidine deaminases","volume":"86","author":"Mahieux","year":"2005","journal-title":"J. Gen. Virol."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1016\/j.virol.2005.01.011","article-title":"Complementary function of the two catalytic domains of APOBEC3G","volume":"333","author":"Navarro","year":"2005","journal-title":"Virology"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1186\/1742-4690-2-32","article-title":"APOBEC3G targets human T-cell leukemia virus type 1","volume":"2","author":"Sasada","year":"2005","journal-title":"Retrovirology"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1016\/0042-6822(84)90170-3","article-title":"Identification of gag and env gene products of human T-cell leukemia virus (HTLV)","volume":"136","author":"Hattori","year":"1984","journal-title":"Virology"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"S85","DOI":"10.1097\/00042560-199600001-00015","article-title":"The HTLV-I envelope glycoproteins: Structure and functions","volume":"13","author":"Delamarre","year":"1996","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"906","DOI":"10.1128\/jvi.66.2.906-913.1992","article-title":"Human T-cell leukemia virus type I envelope protein maturation process: Requirements for syncytium formation","volume":"66","author":"Pique","year":"1992","journal-title":"J. Virol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1006\/viro.1994.1322","article-title":"A truncated HTLV-I envelope protein, lacking the hydrophobic membrane anchor domain, is associated with cellular membranes and virions","volume":"202","author":"Carrington","year":"1994","journal-title":"Virology"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"963","DOI":"10.1128\/JVI.77.2.963-969.2003","article-title":"Human T-cell leukemia virus type 1 envelope-mediated syncytium formation can be activated in resistant Mammalian cell lines by a carboxy-terminal truncation of the envelope cytoplasmic domain","volume":"77","author":"Kim","year":"2003","journal-title":"J. Virol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"8813","DOI":"10.1073\/pnas.89.18.8813","article-title":"Protein isoforms encoded by the pX region of human T-cell leukemia\/lymphotropic virus type I","volume":"89","author":"Koralnik","year":"1992","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"3726","DOI":"10.1182\/blood-2008-04-146928","article-title":"In vivo genetic mutations define predominant functions of the human T-cell leukemia\/lymphoma virus p12I protein","volume":"113","author":"Fukumoto","year":"2009","journal-title":"Blood"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Pise-Masison, C.A., de Castro-Amarante, M.F., Enose-Akahata, Y., Buchmann, R.C., Fenizia, C., Washington Parks, R., Edwards, D., Fiocchi, M., Alcantara, L.C., and Bialuk, I. (2014). Co-dependence of HTLV-1 p12 and p8 functions in virus persistence. PLoS Pathog., 10.","DOI":"10.1371\/journal.ppat.1004454"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"420","DOI":"10.1016\/j.meegid.2016.08.020","article-title":"Analyses of HTLV-1 sequences suggest interaction between ORF-I mutations and HAM\/TSP outcome","volume":"45","author":"Barreto","year":"2016","journal-title":"Infect. Genet. Evol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"899","DOI":"10.1089\/088922202760265560","article-title":"Frequency of p12K and p12R alleles of HTLV Type 1 in HAM\/TSP patients and in asymptomatic HTLV type 1 carriers","volume":"18","author":"Martins","year":"2002","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Afonso, P.V., Fagrouch, Z., Deijs, M., Niphuis, H., Bogers, W., Gessain, A., van der Hoek, L., and Verschoor, E.J. (2019). Absence of accessory genes in a divergent simian T-lymphotropic virus type 1 isolated from a bonnet macaque (Macaca radiata). PLoS Negl. Trop. Dis., 13.","DOI":"10.1371\/journal.pntd.0007521"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"14","DOI":"10.1186\/s12977-024-00647-w","article-title":"High level of genomic divergence in p12 and genes of HTLV-1 subtype-C in Central Australia","volume":"21","author":"Hirons","year":"2024","journal-title":"Retrovirology"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"724","DOI":"10.1016\/j.celrep.2019.09.016","article-title":"The Nature of the HTLV-1 Provirus in Naturally Infected Individuals Analyzed by the Viral DNA-Capture-Seq Approach","volume":"29","author":"Katsuya","year":"2019","journal-title":"Cell Rep."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"37150","DOI":"10.1074\/jbc.M603981200","article-title":"Human T-cell leukemia virus type I p30 nuclear\/nucleolar retention is mediated through interactions with RNA and a constituent of the 60 S ribosomal subunit","volume":"281","author":"Ghorbel","year":"2006","journal-title":"J. Biol. Chem."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"5897","DOI":"10.1182\/blood-2010-08-304600","article-title":"Human T-lymphotropic type 1 virus p30 inhibits homologous recombination and favors unfaithful DNA repair","volume":"117","author":"Baydoun","year":"2011","journal-title":"Blood"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4505","DOI":"10.1038\/sj.onc.1203047","article-title":"Mitochondrial targeting of the p13II protein coded by the x-II ORF of human T-cell leukemia\/lymphotropic virus type I (HTLV-I)","volume":"18","author":"Ciminale","year":"1999","journal-title":"Oncogene"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1182\/blood-2010-06-293340","article-title":"Suppression of HTLV-1 replication by Tax-mediated rerouting of the p13 viral protein to nuclear speckles","volume":"118","author":"Andresen","year":"2011","journal-title":"Blood"},{"key":"ref_89","doi-asserted-by":"crossref","unstructured":"Baratella, M., Forlani, G., Raval, G.U., Tedeschi, A., Gout, O., Gessain, A., Tosi, G., and Accolla, R.S. (2017). Cytoplasmic Localization of HTLV-1 HBZ Protein: A Biomarker of HTLV-1-Associated Myelopathy\/Tropical Spastic Paraparesis (HAM\/TSP). PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005285"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1002\/ijc.2910430227","article-title":"Characterization of HTLV-I isolates and T lymphoid cell lines derived from French West Indian patients with tropical spastic paraparesis","volume":"43","author":"Gessain","year":"1989","journal-title":"Int. J. Cancer"},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Hoshino, H. (2012). Cellular Factors Involved in HTLV-1 Entry and Pathogenicit. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00222"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1038\/nm1745","article-title":"Cell-free HTLV-1 infects dendritic cells leading to transmission and transformation of CD4(+) T cells","volume":"14","author":"Jones","year":"2008","journal-title":"Nat. Med."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Pique, C., and Jones, K.S. (2012). Pathways of cell-cell transmission of HTLV-1. Front. Microbiol., 3.","DOI":"10.3389\/fmicb.2012.00378"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1092","DOI":"10.1089\/aid.2004.20.1092","article-title":"Human T cell lymphotropic virus type I (HTLV-I) p12I is dispensable for HTLV-I transmission and maintenance of infection in vivo","volume":"20","author":"Furukawa","year":"2004","journal-title":"AIDS Res. Hum. Retroviruses"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4701","DOI":"10.1182\/blood.V91.12.4701.412k23_4701_4707","article-title":"Selective ablation of human T-cell lymphotropic virus type 1 p12I reduces viral infectivity in vivo","volume":"91","author":"Collins","year":"1998","journal-title":"Blood"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1016\/j.virol.2003.09.010","article-title":"Roles of viral and cellular proteins in the expression of alternatively spliced HTLV-1 pX mRNAs","volume":"317","author":"Princler","year":"2003","journal-title":"Virology"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"18744","DOI":"10.1074\/jbc.M109087200","article-title":"Heterogeneous nuclear ribonucleoprotein A1 interferes with the binding of the human T cell leukemia virus type 1 rex regulatory protein to its response element","volume":"277","author":"Dodon","year":"2002","journal-title":"J. Biol. Chem."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"2810","DOI":"10.1128\/jvi.71.4.2810-2818.1997","article-title":"Inhibition of human T-cell leukemia virus type 2 Rex function by truncated forms of Rex encoded in alternatively spliced mRNAs","volume":"71","author":"Ciminale","year":"1997","journal-title":"J. Virol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"4623","DOI":"10.1128\/JVI.00839-10","article-title":"Association of SRC-related kinase Lyn with the interleukin-2 receptor and its role in maintaining constitutive phosphorylation of JAK\/STAT in human T-cell leukemia virus type 1-transformed T cells","volume":"85","author":"Shuh","year":"2011","journal-title":"J. Virol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"4559","DOI":"10.1128\/JVI.06361-11","article-title":"Nuclear export and expression of human T-cell leukemia virus type 1 tax\/rex mRNA are RxRE\/Rex dependent","volume":"86","author":"Bai","year":"2012","journal-title":"J. Virol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/j.micinf.2013.03.006","article-title":"Viral interference with host mRNA surveillance, the nonsense-mediated mRNA decay (NMD) pathway, through a new function of HTLV-1 Rex: Implications for retroviral replication","volume":"15","author":"Nakano","year":"2013","journal-title":"Microbes Infect."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/11\/1755\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:29:25Z","timestamp":1760113765000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/16\/11\/1755"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,11,9]]},"references-count":101,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2024,11]]}},"alternative-id":["v16111755"],"URL":"https:\/\/doi.org\/10.3390\/v16111755","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,11,9]]}}}