{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,2]],"date-time":"2026-05-02T08:27:36Z","timestamp":1777710456725,"version":"3.51.4"},"update-to":[{"DOI":"10.1371\/journal.ppat.1011494","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000}}],"reference-count":113,"publisher":"Public Library of Science (PLoS)","issue":"7","license":[{"start":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T00:00:00Z","timestamp":1690761600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["102126"],"award-info":[{"award-number":["102126"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["207477"],"award-info":[{"award-number":["207477"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100014013","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["MC-A658-5TY10"],"award-info":[{"award-number":["MC-A658-5TY10"]}],"id":[{"id":"10.13039\/100014013","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["206292\/Z\/17\/Z"],"award-info":[{"award-number":["206292\/Z\/17\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013342","name":"NIHR Imperial Biomedical Research Centre","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100013342","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>\n                    Infections by Human T cell Leukaemia Virus type 1 (HTLV-1) persist for the lifetime of the host by integrating into the genome of CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells. Proviral gene expression is essential for proviral survival and the maintenance of the proviral load, through the pro-proliferative changes it induces in infected cells. Despite their role in HTLV-1 infection and a persistent cytotoxic T lymphocyte response raised against the virus, proviral transcripts from the sense-strand are rarely detected in fresh cells extracted from the peripheral blood, and have recently been found to be expressed intermittently by a small subset of cells at a given time.\n                    <jats:italic>Ex vivo<\/jats:italic>\n                    culture of infected cells prompts synchronised proviral expression in infected cells from peripheral blood, allowing the study of factors involved in reactivation in primary cells. Here, we used bulk RNA-seq to examine the host transcriptome over six days\n                    <jats:italic>in vitro<\/jats:italic>\n                    , following proviral reactivation in primary peripheral CD4\n                    <jats:sup>+<\/jats:sup>\n                    T cells isolated from subjects with non-malignant HTLV-1 infection. Infected cells displayed a conserved response to reactivation, characterised by discrete stages of gene expression, cell division and subsequently horizontal transmission of the virus. We observed widespread changes in Polycomb gene expression following reactivation, including an increase in PRC2 transcript levels and diverse changes in the expression of PRC1 components. We hypothesize that these transcriptional changes constitute a negative feedback loop that maintains proviral latency by re-deposition of H2AK119ub1 following the end of proviral expression. Using RNAi, we found that certain deubiquitinases,\n                    <jats:italic>BAP1<\/jats:italic>\n                    ,\n                    <jats:italic>USP14<\/jats:italic>\n                    and\n                    <jats:italic>OTUD5<\/jats:italic>\n                    each promote proviral transcription. These data demonstrate the detailed trajectory of HTLV-1 proviral reactivation in primary HTLV-1-carrier lymphocytes and the impact on the host cell.\n                  <\/jats:p>","DOI":"10.1371\/journal.ppat.1011494","type":"journal-article","created":{"date-parts":[[2023,7,31]],"date-time":"2023-07-31T13:33:58Z","timestamp":1690810438000},"page":"e1011494","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":6,"title":["The transcriptome of HTLV-1-infected primary cells following reactivation reveals changes to host gene expression central to the proviral life cycle"],"prefix":"10.1371","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3266-4499","authenticated-orcid":true,"given":"Aris E. N.","family":"Aristodemou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4657-6323","authenticated-orcid":true,"given":"David S.","family":"Rueda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Graham P.","family":"Taylor","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2624-3599","authenticated-orcid":true,"given":"Charles R. M.","family":"Bangham","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2023,7,31]]},"reference":[{"key":"ppat.1011494.ref001","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","author":"BJ Poiesz","year":"1980","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ppat.1011494.ref002","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1002\/(SICI)1097-0215(20000201)85:3<319::AID-IJC4>3.0.CO;2-B","article-title":"Evaluation of adult T-cell leukemia\/lymphoma incidence and its impact on non-Hodgkin lymphoma incidence in southwestern Japan","volume":"85","author":"K Arisawa","year":"2000","journal-title":"Int J Cancer"},{"key":"ppat.1011494.ref003","first-page":"1096","article-title":"The risk of development of HTLV-I-associated myelopathy\/tropical spastic paraparesis among persons infected with HTLV-I","volume":"3","author":"JE Kaplan","year":"1990","journal-title":"J Acquir Immune Defic Syndr"},{"key":"ppat.1011494.ref004","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1097\/00042560-199802010-00011","article-title":"Incidence of HTLV-I-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) in Jamaica and Trinidad","volume":"17","author":"EM Maloney","year":"1998","journal-title":"J Acquir Immune Defic Syndr Hum Retrovirology Off Publ Int Retrovirology Assoc"},{"key":"ppat.1011494.ref005","doi-asserted-by":"crossref","first-page":"1211","DOI":"10.1182\/blood-2009-12-257410","article-title":"Human T-cell Leukemia Virus type I (HTLV-1) proviral load and disease progression in asymptomatic HTLV-1 carriers: a nationwide prospective study in Japan","author":"M Iwanaga","year":"2010","journal-title":"Blood"},{"key":"ppat.1011494.ref006","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","author":"KJM Jeffery","year":"1999","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ppat.1011494.ref007","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","author":"M Nagai","year":"1998","journal-title":"Journal of neurovirology"},{"key":"ppat.1011494.ref008","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1016\/0042-6822(92)90517-S","article-title":"Activated, HTLV-1-specific cytotoxic T-lymphocytes are found in healthy seropositives as well as in patients with tropical spastic paraparesis","author":"CE Parker","year":"1992","journal-title":"Virology"},{"key":"ppat.1011494.ref009","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","author":"A Gessain","year":"1991","journal-title":"Journal of virology"},{"key":"ppat.1011494.ref010","article-title":"Single-cell heterogeneity and cell-cycle-related viral gene bursts in the human leukaemia virus HTLV-1","author":"MR Billman","year":"2017","journal-title":"Wellcome open research"},{"key":"ppat.1011494.ref011","doi-asserted-by":"crossref","first-page":"e1008164","DOI":"10.1371\/journal.ppat.1008164","article-title":"Kinetics of HTLV-1 reactivation from latency quantified by single-molecule RNA FISH and stochastic modelling","author":"M Miura","year":"2019","journal-title":"PLOS Pathogens"},{"key":"ppat.1011494.ref012","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","author":"Y Satou","year":"2006","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"ppat.1011494.ref013","doi-asserted-by":"crossref","first-page":"e1001117","DOI":"10.1371\/journal.ppat.1001117","article-title":"HLA class I binding of HBZ determines outcome in HTLV-1 infection","author":"A MacNamara","year":"2010","journal-title":"PLoS pathogens"},{"key":"ppat.1011494.ref014","first-page":"1095","article-title":"Protective effect of cytotoxic T lymphocytes targeting HTLV-1 bZIP factor","volume":"126","author":"K Sugata","year":"2015","journal-title":"Blood J Am Soc Hematol"},{"key":"ppat.1011494.ref015","doi-asserted-by":"crossref","first-page":"1386","DOI":"10.1182\/blood.V95.4.1386.004k22_1386_1392","article-title":"Abundant tax protein expression in CD4 T cells infected with Human T-cell Lymphotropic Virus type I (HTLV-I) is prevented by cytotoxic T lymphocytes","author":"E Hanon","year":"2000","journal-title":"Blood"},{"key":"ppat.1011494.ref016","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/0022-510X(88)90248-1","article-title":"Expression of HTLV-I antigen in cultured peripheral blood mononuclear cells from patients with HTLV-I associated myelopathy","volume":"87","author":"S Minato","year":"1988","journal-title":"J Neurol Sci"},{"key":"ppat.1011494.ref017","doi-asserted-by":"crossref","first-page":"4855","DOI":"10.1182\/blood-2010-11-316463","article-title":"Kinetics and intracellular compartmentalization of HTLV-1 gene expression: nuclear retention of HBZ mRNAs","author":"F Rende","year":"2011","journal-title":"Blood"},{"key":"ppat.1011494.ref018","doi-asserted-by":"crossref","first-page":"684","DOI":"10.1016\/j.coviro.2013.08.010","article-title":"Human T-cell Leukemia Virus type 1: replication, proliferation and propagation by Tax and HTLV-1 bZIP factor","author":"M Matsuoka","year":"2013","journal-title":"Current opinion in virology"},{"key":"ppat.1011494.ref019","doi-asserted-by":"crossref","first-page":"5986","DOI":"10.1038\/sj.onc.1208976","article-title":"Impact of HTLV-I Tax on cell cycle progression and the cellular DNA damage repair response","volume":"24","author":"SJ Marriott","year":"2005","journal-title":"Oncogene"},{"key":"ppat.1011494.ref020","article-title":"Sporadic on\/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells","author":"M Mahgoub","year":"2018","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ppat.1011494.ref021","first-page":"715","article-title":"HTLV-1 Tax oncoprotein stimulates ROS production and apoptosis in T cells by interacting with USP10","volume":"122","author":"M Takahashi","year":"2013","journal-title":"Blood J Am Soc Hematol"},{"key":"ppat.1011494.ref022","doi-asserted-by":"crossref","first-page":"e1010387","DOI":"10.1371\/journal.ppat.1010387","article-title":"Time-course of host cell transcription during the HTLV-1 transcriptional burst","volume":"18","author":"H Kiik","year":"2022","journal-title":"PLoS Pathog"},{"key":"ppat.1011494.ref023","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12977-020-0511-0","article-title":"HTLV-1 bZIP factor: the key viral gene for pathogenesis","volume":"17","author":"M Matsuoka","year":"2020","journal-title":"Retrovirology"},{"key":"ppat.1011494.ref024","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","author":"G Belrose","year":"2011","journal-title":"Blood"},{"key":"ppat.1011494.ref025","doi-asserted-by":"crossref","first-page":"e1009577","DOI":"10.1371\/journal.ppat.1009577","article-title":"Epigenomic regulation of human T-cell leukemia virus by chromatin-insulator CTCF","volume":"17","author":"X Cheng","year":"2021","journal-title":"PLoS Pathog"},{"key":"ppat.1011494.ref026","article-title":"Histone H2A monoubiquitylation and p38-MAPKs regulate immediate-early gene-like reactivation of latent retrovirus HTLV-1","author":"A Kulkarni","year":"2018","journal-title":"JCI Insight"},{"key":"ppat.1011494.ref027","first-page":"1387.e3","article-title":"Glucose Metabolism and Oxygen Availability Govern Reactivation of the Latent Human Retrovirus HTLV-1","author":"A Kulkarni","year":"2017","journal-title":"Cell chemical biology"},{"key":"ppat.1011494.ref028","article-title":"Spontaneous HTLV-1 transcription is accompanied by distinct epigenetic changes in the 5\u2019 and 3\u2019 long terminal repeats","author":"M Miura","year":"2018","journal-title":"Wellcome open research"},{"key":"ppat.1011494.ref029","doi-asserted-by":"crossref","first-page":"3054","DOI":"10.1073\/pnas.1423199113","article-title":"The retrovirus HTLV-1 inserts an ectopic CTCF-binding site into the human genome","author":"Y Satou","year":"2016","journal-title":"Proceedings of the National Academy of Sciences"},{"key":"ppat.1011494.ref030","doi-asserted-by":"crossref","first-page":"815","DOI":"10.1038\/s41580-021-00398-y","article-title":"The molecular principles of gene regulation by Polycomb repressive complexes","volume":"22","author":"NP Blackledge","year":"2021","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ppat.1011494.ref031","doi-asserted-by":"crossref","first-page":"66","DOI":"10.1038\/s41408-021-00458-8","article-title":"Quantification of T cell clonality in human T cell leukaemia virus type-1 carriers can detect the development of adult T cell leukaemia early","volume":"11","author":"SN Wolf","year":"2021","journal-title":"Blood Cancer J"},{"key":"ppat.1011494.ref032","doi-asserted-by":"crossref","first-page":"e1005560","DOI":"10.1371\/journal.ppat.1005560","article-title":"CADM1\/TSLC1 identifies HTLV-1-infected cells and determines their susceptibility to CTL-mediated lysis","author":"K Manivannan","year":"2016","journal-title":"PLoS pathogens"},{"key":"ppat.1011494.ref033","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":"H Katsuya","year":"2019","journal-title":"Cell Rep"},{"key":"ppat.1011494.ref034","doi-asserted-by":"crossref","first-page":"3488","DOI":"10.1182\/blood-2012-07-445593","article-title":"HTLV-1\u2013infected T cells contain a single integrated provirus in natural infection","author":"LB Cook","year":"2012","journal-title":"Blood"},{"key":"ppat.1011494.ref035","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1016\/j.cell.2018.04.005","article-title":"A post-transcriptional feedback mechanism for noise suppression and fate stabilization","volume":"173","author":"MM Hansen","year":"2018","journal-title":"Cell"},{"key":"ppat.1011494.ref036","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: ultrafast universal RNA-seq aligner","volume":"29","author":"A Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ppat.1011494.ref037","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"NL Bray","year":"2016","journal-title":"Nat Biotechnol"},{"key":"ppat.1011494.ref038","first-page":"1","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"MI Love","year":"2014","journal-title":"Genome Biol"},{"key":"ppat.1011494.ref039","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1089\/omi.2011.0118","article-title":"clusterProfiler: an R package for comparing biological themes among gene clusters","volume":"16","author":"G Yu","year":"2012","journal-title":"Omics J Integr Biol"},{"key":"ppat.1011494.ref040","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene ontology: tool for the unification of biology","volume":"25","author":"M Ashburner","year":"2000","journal-title":"Nat Genet"},{"key":"ppat.1011494.ref041","doi-asserted-by":"crossref","first-page":"D325","DOI":"10.1093\/nar\/gkaa1113","article-title":"The Gene Ontology resource: enriching a GOld mine","volume":"49","author":"The Gene Ontology Consortium","year":"2021","journal-title":"Nucleic Acids Res"},{"key":"ppat.1011494.ref042","doi-asserted-by":"crossref","first-page":"D1140","DOI":"10.1093\/nar\/gku1092","article-title":"Cyclebase 3.0: a multi-organism database on cell-cycle regulation and phenotypes","volume":"43","author":"A Santos","year":"2015","journal-title":"Nucleic Acids Res"},{"key":"ppat.1011494.ref043","doi-asserted-by":"crossref","first-page":"1713","DOI":"10.1126\/science.1080115","article-title":"Spread of HTLV-I between lymphocytes by virus-induced polarization of the cytoskeleton","author":"T Igakura","year":"2003","journal-title":"Science"},{"key":"ppat.1011494.ref044","doi-asserted-by":"crossref","first-page":"2147","DOI":"10.3389\/fmicb.2019.02147","article-title":"HTLV-1 extracellular vesicles promote cell-to-cell contact","author":"DO Pinto","year":"2019","journal-title":"Front Microbiol"},{"key":"ppat.1011494.ref045","doi-asserted-by":"crossref","first-page":"7672","DOI":"10.1128\/JVI.75.16.7672-7682.2001","article-title":"Endoplasmic reticulum and cis-Golgi localization of human T-lymphotropic virus type 1 p12I: association with calreticulin and calnexin","volume":"75","author":"W Ding","year":"2001","journal-title":"J Virol"},{"key":"ppat.1011494.ref046","doi-asserted-by":"crossref","first-page":"34424","DOI":"10.1074\/jbc.M203023200","article-title":"Mitochondrial alterations induced by the p13II protein of human T-cell leukemia virus type 1: critical role of arginine residues","volume":"277","author":"DM D\u2019Agostino","year":"2002","journal-title":"J Biol Chem"},{"key":"ppat.1011494.ref047","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1016\/j.bbabio.2009.02.001","article-title":"Modulation of mitochondrial K+ permeability and reactive oxygen species production by the p13 protein of human T-cell leukemia virus type 1","volume":"1787","author":"M Silic-Benussi","year":"2009","journal-title":"Biochim Biophys Acta BBA-Bioenerg"},{"key":"ppat.1011494.ref048","doi-asserted-by":"crossref","first-page":"74","DOI":"10.3390\/v8030074","article-title":"Molecular mechanisms of HTLV-1 cell-to-cell transmission","volume":"8","author":"C Gross","year":"2016","journal-title":"Viruses"},{"key":"ppat.1011494.ref049","doi-asserted-by":"crossref","first-page":"418","DOI":"10.1002\/ijc.2910520316","article-title":"Strong induction of ICAM-1 in human T cells transformed by human T-cell-leukemia virus type 1 and depression of ICAM-1 or LFA-1 in adult T-cell-leukemia-derived cell lines","volume":"52","author":"K Fukudome","year":"1992","journal-title":"Int J Cancer"},{"key":"ppat.1011494.ref050","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1016\/j.cels.2015.12.004","article-title":"The molecular signatures database hallmark gene set collection","volume":"1","author":"A Liberzon","year":"2015","journal-title":"Cell Syst"},{"key":"ppat.1011494.ref051","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1038\/s41556-018-0205-1","article-title":"mTOR as a central hub of nutrient signalling and cell growth","volume":"21","author":"J Kim","year":"2019","journal-title":"Nat Cell Biol"},{"key":"ppat.1011494.ref052","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1038\/nrc3984","article-title":"MYC: connecting selective transcriptional control to global RNA production","volume":"15","author":"TR Kress","year":"2015","journal-title":"Nat Rev Cancer"},{"key":"ppat.1011494.ref053","doi-asserted-by":"crossref","first-page":"2274","DOI":"10.1016\/j.cub.2014.08.007","article-title":"The mTORC1\/S6K1 pathway regulates glutamine metabolism through the eIF4B-dependent control of c-Myc translation","volume":"24","author":"A Csibi","year":"2014","journal-title":"Curr Biol"},{"key":"ppat.1011494.ref054","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1038\/s41580-020-0250-z","article-title":"Mechanisms, regulation and functions of the unfolded protein response","volume":"21","author":"C Hetz","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"ppat.1011494.ref055","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.cotox.2017.11.002","article-title":"NF-\u03baB in oxidative stress","volume":"7","author":"K. Lingappan","year":"2018","journal-title":"Curr Opin Toxicol"},{"key":"ppat.1011494.ref056","doi-asserted-by":"crossref","first-page":"16288","DOI":"10.1016\/S0021-9258(18)41998-9","article-title":"Transactivation of the c-myc promoter by human T cell leukemia virus type 1 tax is mediated by NF kappa B","volume":"267","author":"M Duyao","year":"1992","journal-title":"J Biol Chem"},{"key":"ppat.1011494.ref057","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fmicb.2018.00285","article-title":"HTLV deregulation of the NF-\u03baB pathway: An update on tax and antisense proteins role","volume":"9","author":"S Fochi","year":"2018","journal-title":"Front Microbiol"},{"key":"ppat.1011494.ref058","doi-asserted-by":"crossref","first-page":"4343","DOI":"10.1128\/JVI.02054-07","article-title":"XBP-1, a novel human T-lymphotropic virus type 1 (HTLV-1) tax binding protein, activates HTLV-1 basal and tax-activated transcription","volume":"82","author":"SC Ku","year":"2008","journal-title":"J Virol"},{"key":"ppat.1011494.ref059","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1111\/j.1349-7006.2011.02123.x","article-title":"Activation of mTOR by human T-cell leukemia virus type 1 Tax is important for the transformation of mouse T cells to interleukin-2-independent growth","volume":"103","author":"M Yoshita","year":"2012","journal-title":"Cancer Sci"},{"key":"ppat.1011494.ref060","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: a practical and powerful approach to multiple testing","volume":"57","author":"Y Benjamini","year":"1995","journal-title":"J R Stat Soc Ser B Methodol"},{"key":"ppat.1011494.ref061","doi-asserted-by":"crossref","first-page":"e21064","DOI":"10.7554\/eLife.21064","article-title":"PCGF6-PRC1 suppresses premature differentiation of mouse embryonic stem cells by regulating germ cell-related genes","volume":"6","author":"M Endoh","year":"2017","journal-title":"Elife"},{"key":"ppat.1011494.ref062","doi-asserted-by":"crossref","first-page":"6267","DOI":"10.1158\/0008-5472.CAN-17-0570","article-title":"ASXL3 is a novel pluripotency factor in human respiratory epithelial cells and a potential therapeutic target in small cell lung cancer","volume":"77","author":"V Shukla","year":"2017","journal-title":"Cancer Res"},{"key":"ppat.1011494.ref063","first-page":"E51","article-title":"The histone H2A deubiquitinase Usp16 regulates hematopoiesis and hematopoietic stem cell function","volume":"113","author":"Y Gu","year":"2016","journal-title":"Proc Natl Acad Sci"},{"key":"ppat.1011494.ref064","first-page":"1","article-title":"The histone H2A deubiquitinase Usp16 regulates embryonic stem cell gene expression and lineage commitment","volume":"5","author":"W Yang","year":"2014","journal-title":"Nat Commun"},{"key":"ppat.1011494.ref065","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1002\/ijc.2910360102","article-title":"Effect of human serum anti-HTLV antibodies on viral antigen induction in in vitro cultured peripheral lymphocytes from adult T-cell leukemia patients and healthy virus carriers","volume":"36","author":"T Tochikura","year":"1985","journal-title":"Int J Cancer"},{"key":"ppat.1011494.ref066","doi-asserted-by":"crossref","first-page":"8035","DOI":"10.1073\/pnas.0608832104","article-title":"In vivo T lymphocyte dynamics in humans and the impact of human T-lymphotropic virus 1 infection","volume":"104","author":"B Asquith","year":"2007","journal-title":"Proc Natl Acad Sci"},{"key":"ppat.1011494.ref067","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1146\/annurev-virology-092818-015501","article-title":"Regulation of latency in the human T cell leukemia virus, HTLV-1","volume":"6","author":"CR Bangham","year":"2019","journal-title":"Annu Rev Virol"},{"key":"ppat.1011494.ref068","first-page":"2419","article-title":"Proliferation of HTLV-1 infected circulating cells in vivo in all asymptomatic carriers and patients with TSP\/HAM","volume":"12","author":"M Cavrois","year":"1996","journal-title":"Oncogene"},{"key":"ppat.1011494.ref069","doi-asserted-by":"crossref","first-page":"1012","DOI":"10.1182\/blood.V80.4.1012.1012","article-title":"Frequent clonal proliferation of human T-cell leukemia virus type 1 (HTLV-1)-infected T cells in HTLV-1-associated myelopathy (HAM-TSP)","volume":"80","author":"Y Furukawa","year":"1992","journal-title":"Blood"},{"key":"ppat.1011494.ref070","doi-asserted-by":"crossref","first-page":"e1004040","DOI":"10.1371\/journal.ppat.1004040","article-title":"Regulation of Human T-Lymphotropic Virus Type I Latency and Reactivation by HBZ and Rex","author":"S Philip","year":"2014","journal-title":"PLoS Pathogens"},{"key":"ppat.1011494.ref071","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1182\/blood-2004-07-2850","article-title":"Engagement of specific T-cell surface molecules regulates cytoskeletal polarization in HTLV-1\u2013infected lymphocytes","volume":"106","author":"AL Barnard","year":"2005","journal-title":"Blood"},{"key":"ppat.1011494.ref072","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1080\/22221751.2020.1752117","article-title":"Multiple recombinant events in human T-cell leukemia virus type 1: complete sequences of recombinant African strains","volume":"9","author":"O Cassar","year":"2020","journal-title":"Emerg Microbes Infect"},{"key":"ppat.1011494.ref073","doi-asserted-by":"crossref","first-page":"9782","DOI":"10.1128\/JVI.01591-14","article-title":"Northern African strains of human T-lymphotropic virus type 1 arose from a recombination event","volume":"88","author":"A Desrames","year":"2014","journal-title":"J Virol"},{"key":"ppat.1011494.ref074","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/1742-4690-2-52","article-title":"Retroviral superinfection resistance","volume":"2","author":"M Nethe","year":"2005","journal-title":"Retrovirology"},{"key":"ppat.1011494.ref075","first-page":"1652","article-title":"HTLV-I tax induces cellular proteins that activate the \u03baB element in the IL-2 receptor \u03b1 gene","volume":"241","author":"DW Ballard","year":"1988","journal-title":"Science"},{"key":"ppat.1011494.ref076","doi-asserted-by":"crossref","first-page":"6805","DOI":"10.1093\/emboj\/20.23.6805","article-title":"Retroviral oncoprotein Tax induces processing of NF-\u03baB2\/p100 in T cells: evidence for the involvement of IKK\u03b1","volume":"20","author":"G Xiao","year":"2001","journal-title":"EMBO J"},{"key":"ppat.1011494.ref077","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1016\/j.leukres.2006.08.001","article-title":"Longitudinal inhibition of PI3K\/Akt\/mTOR signaling by LY294002 and rapamycin induces growth arrest of adult T-cell leukemia cells","volume":"31","author":"T Ikezoe","year":"2007","journal-title":"Leuk Res"},{"key":"ppat.1011494.ref078","doi-asserted-by":"crossref","first-page":"2317","DOI":"10.1038\/onc.2013.181","article-title":"HTLV-1 HBZ positively regulates the mTOR signaling pathway via inhibition of GADD34 activity in the cytoplasm","volume":"33","author":"R Mukai","year":"2014","journal-title":"Oncogene"},{"key":"ppat.1011494.ref079","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1182\/blood-2008-06-161729","article-title":"Human T-cell Leukemia Virus type 1 bZIP factor selectively suppresses the classical pathway of NF-\u03baB","author":"T Zhao","year":"2009","journal-title":"Blood"},{"key":"ppat.1011494.ref080","first-page":"2360","article-title":"Constitutive activation of NF-\u03baB in primary adult T-cell leukemia cells","volume":"93","author":"N Mori","year":"1999","journal-title":"Blood J Am Soc Hematol"},{"key":"ppat.1011494.ref081","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1038\/ng.3415","article-title":"Integrated molecular analysis of adult T cell leukemia\/lymphoma","author":"K Kataoka","year":"2015","journal-title":"Nature genetics"},{"key":"ppat.1011494.ref082","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":"AG Rowan","year":"2020","journal-title":"Blood"},{"key":"ppat.1011494.ref083","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/j.celrep.2014.05.053","article-title":"Transcription factors modulate c-Fos transcriptional bursts","author":"A Senecal","year":"2014","journal-title":"Cell reports"},{"key":"ppat.1011494.ref084","doi-asserted-by":"crossref","first-page":"eabg0791","DOI":"10.1126\/sciimmunol.abg0791","article-title":"Activation of mTORC1 at late endosomes misdirects T cell fate decision in older individuals","volume":"6","author":"J Jin","year":"2021","journal-title":"Sci Immunol"},{"key":"ppat.1011494.ref085","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1007\/s10875-009-9296-6","article-title":"NF-\u03baB signaling in the aging process","volume":"29","author":"A Salminen","year":"2009","journal-title":"J Clin Immunol"},{"key":"ppat.1011494.ref086","doi-asserted-by":"crossref","unstructured":"Corradin A, Camillo BD, Rende F, Ciminale V, Toffolo G, Cobelli C. Retrovirus HTLV-1 Gene Circuit: A Potential Oscillator for Eukaryotes. In: Altman RB, Dunker AK, Hunter L, Murray T, Klein TE, editors. Biocomputing 2010: Proceedings of the Pacific Symposium, Kamuela, Hawaii, USA, 4\u20138 January 2010. World Scientific Publishing; 2010. pp. 421\u2013432. http:\/\/psb.stanford.edu\/psb-online\/proceedings\/psb10\/corradin.pdf","DOI":"10.1142\/9789814295291_0044"},{"key":"ppat.1011494.ref087","first-page":"1790","article-title":"Polycomb-dependent epigenetic landscape in adult T-cell leukemia","volume":"127","author":"D Fujikawa","year":"2016","journal-title":"Blood J Am Soc Hematol"},{"key":"ppat.1011494.ref088","doi-asserted-by":"crossref","first-page":"121","DOI":"10.1016\/j.ccr.2011.12.015","article-title":"Polycomb-mediated loss of miR-31 activates NIK-dependent NF-\u03baB pathway in adult T cell leukemia and other cancers","volume":"21","author":"M Yamagishi","year":"2012","journal-title":"Cancer Cell"},{"key":"ppat.1011494.ref089","article-title":"A bivalent chromatin structure marks key developmental genes in embryonic stem cells","author":"BE Bernstein","year":"2006","journal-title":"Cell"},{"key":"ppat.1011494.ref090","doi-asserted-by":"crossref","first-page":"110332","DOI":"10.1016\/j.celrep.2022.110332","article-title":"Bivalent-histone-marked immediate-early gene regulation is vital for VEGF-responsive angiogenesis","volume":"38","author":"Y Kanki","year":"2022","journal-title":"Cell Rep"},{"key":"ppat.1011494.ref091","doi-asserted-by":"crossref","first-page":"2048","DOI":"10.1128\/JVI.01264-08","article-title":"Upregulation of Human T-cell Leukemia Virus type 1 antisense transcription by the viral tax protein","volume":"83","author":"S Landry","year":"2009","journal-title":"J Virol"},{"key":"ppat.1011494.ref092","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","author":"M Yoshida","year":"2008","journal-title":"Journal of virology"},{"key":"ppat.1011494.ref093","doi-asserted-by":"crossref","first-page":"3526","DOI":"10.1016\/j.molcel.2021.06.020","article-title":"BAP1 enhances Polycomb repression by counteracting widespread H2AK119ub1 deposition and chromatin condensation","volume":"81","author":"E Conway","year":"2021","journal-title":"Mol Cell"},{"key":"ppat.1011494.ref094","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1038\/nature09299","article-title":"Enhancement of proteasome activity by a small-molecule inhibitor of USP14","volume":"467","author":"B-H Lee","year":"2010","journal-title":"Nature"},{"key":"ppat.1011494.ref095","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1146\/annurev.cb.10.110194.002201","article-title":"Structure, regulation and function of NF-kappaB","volume":"10","author":"U Siebenlist","year":"1994","journal-title":"Annu Rev Cell Biol"},{"key":"ppat.1011494.ref096","doi-asserted-by":"crossref","first-page":"1827","DOI":"10.3389\/fimmu.2017.01827","article-title":"Ubiquitin-specific protease 14 negatively regulates toll-like receptor 4-mediated signaling and autophagy induction by inhibiting ubiquitination of TAK1-binding protein 2 and Beclin 1","volume":"8","author":"Y Min","year":"2017","journal-title":"Front Immunol"},{"key":"ppat.1011494.ref097","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1002\/iid3.465","article-title":"Inhibiting USP14 ameliorates inflammatory responses in trophoblast cells by suppressing MAPK\/NF-\u03baB signaling","volume":"9","author":"Y Zhao","year":"2021","journal-title":"Immun Inflamm Dis"},{"key":"ppat.1011494.ref098","doi-asserted-by":"crossref","first-page":"eabe2116","DOI":"10.1126\/sciadv.abe2116","article-title":"Linkage-specific deubiquitylation by OTUD5 defines an embryonic pathway intolerant to genomic variation","volume":"7","author":"DB Beck","year":"2021","journal-title":"Sci Adv"},{"key":"ppat.1011494.ref099","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1186\/1471-2199-8-113","article-title":"Relative quantification of mRNA: comparison of methods currently used for real-time PCR data analysis","author":"\u0160 \u010ciko\u0161","year":"2007","journal-title":"BMC molecular biology"},{"key":"ppat.1011494.ref100","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":"J Fan","year":"2010","journal-title":"J Virol"},{"key":"ppat.1011494.ref101","unstructured":"R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria: R Foundation for Statistical Computing; 2021. https:\/\/www.R-project.org\/"},{"key":"ppat.1011494.ref102","doi-asserted-by":"crossref","first-page":"1184","DOI":"10.1038\/nprot.2009.97","article-title":"Mapping identifiers for the integration of genomic datasets with the R\/Bioconductor package biomaRt","volume":"4","author":"S Durinck","year":"2009","journal-title":"Nat Protoc"},{"key":"ppat.1011494.ref103","doi-asserted-by":"crossref","first-page":"3439","DOI":"10.1093\/bioinformatics\/bti525","article-title":"BioMart and Bioconductor: a powerful link between biological databases and microarray data analysis","volume":"21","author":"S Durinck","year":"2005","journal-title":"Bioinformatics"},{"key":"ppat.1011494.ref104","unstructured":"Carlson M. org.Hs.eg.db: Genome wide annotation for Human. 2021."},{"key":"ppat.1011494.ref105","doi-asserted-by":"crossref","DOI":"10.14440\/jbm.2014.36","article-title":"Advanced methods of microscope control using \u03bcManager software","volume":"1","author":"AD Edelstein","year":"2014","journal-title":"J Biol Methods"},{"key":"ppat.1011494.ref106","doi-asserted-by":"crossref","first-page":"W636","DOI":"10.1093\/nar\/gkz268","article-title":"The EMBL-EBI search and sequence analysis tools APIs in 2019","volume":"47","author":"F Madeira","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"ppat.1011494.ref107","doi-asserted-by":"crossref","first-page":"539","DOI":"10.1038\/msb.2011.75","article-title":"Fast, scalable generation of high-quality protein multiple sequence alignments using Clustal Omega","volume":"7","author":"F Sievers","year":"2011","journal-title":"Mol Syst Biol"},{"key":"ppat.1011494.ref108","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.1093\/bioinformatics\/btp033","article-title":"Jalview Version 2\u2014a multiple sequence alignment editor and analysis workbench","volume":"25","author":"AM Waterhouse","year":"2009","journal-title":"Bioinformatics"},{"key":"ppat.1011494.ref109","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","article-title":"FIMO: scanning for occurrences of a given motif","volume":"27","author":"CE Grant","year":"2011","journal-title":"Bioinformatics"},{"key":"ppat.1011494.ref110","doi-asserted-by":"crossref","first-page":"D165","DOI":"10.1093\/nar\/gkab1113","article-title":"JASPAR 2022: the 9th release of the open-access database of transcription factor binding profiles","volume":"50","author":"JA Castro-Mondragon","year":"2022","journal-title":"Nucleic Acids Res"},{"key":"ppat.1011494.ref111","doi-asserted-by":"crossref","DOI":"10.1007\/978-0-387-98141-3","volume-title":"ggplot2: Elegant Graphics for Data Analysis","author":"H. Wickham","year":"2009"},{"key":"ppat.1011494.ref112","doi-asserted-by":"crossref","first-page":"e36245","DOI":"10.7554\/eLife.36245","article-title":"The human leukemia virus HTLV-1 alters the structure and transcription of host chromatin in cis","author":"A Melamed","year":"2018","journal-title":"eLife"},{"key":"ppat.1011494.ref113","doi-asserted-by":"crossref","first-page":"3645","DOI":"10.1093\/bioinformatics\/btx469","article-title":"ggseqlogo: a versatile R package for drawing sequence logos","volume":"33","author":"O. Wagih","year":"2017","journal-title":"Bioinformatics"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1011494","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2023,8,16]],"date-time":"2023-08-16T00:00:00Z","timestamp":1692144000000}}],"container-title":["PLOS Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011494","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,25]],"date-time":"2024-10-25T07:42:19Z","timestamp":1729842139000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.ppat.1011494"}},"subtitle":[],"editor":[{"given":"Patrick L.","family":"Green","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2023,7,31]]},"references-count":113,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2023,7,31]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.ppat.1011494","relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.01.08.523159","asserted-by":"object"}]},"ISSN":["1553-7374"],"issn-type":[{"value":"1553-7374","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,7,31]]}}}