{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,7,30]],"date-time":"2025-07-30T16:02:28Z","timestamp":1753891348818,"version":"3.41.2"},"reference-count":81,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,10]],"date-time":"2023-08-10T00:00:00Z","timestamp":1691625600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Microbiol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Infection with human T cell lymphotropic virus type 1 (HTLV-1) is endemic in Brazil and is linked with pro-inflammatory conditions including HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP), a chronic neuroinflammatory incapacitating disease that culminates in loss of motor functions. The mechanisms underlying the onset and progression of HAM\/TSP are incompletely understood. Previous studies have demonstrated that inflammation and infectious agents can affect the expression of cellular prion protein (PrP<jats:sup>C<\/jats:sup>) in immune cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Here, we investigated whether HTLV-1 infection affected PrP<jats:sup>C<\/jats:sup> content in cell lines and primary CD4<jats:sup>+<\/jats:sup>cells <jats:italic>in vitro<\/jats:italic> using flow cytometry and western blot assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found that HTLV-1 infection decreased the expression levels of PrP<jats:sup>C<\/jats:sup> and HTLV-1 <jats:italic>Orf I<\/jats:italic> encoded p12, an endoplasmic reticulum resident protein also known to affect post-transcriptionally cellular proteins such as MHC-class I and the IL-2 receptor. In addition, we observed a reduced percentage of CD4<jats:sup>+<\/jats:sup> T cells from infected individuals expressing PrP<jats:sup>C<\/jats:sup>, which was reflected by IFN type II but not IL-17 expression.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These results suggested that PrP<jats:sup>C<\/jats:sup> downregulation, linked to both HTLV-1 p12 and IFN-\u03b3 expression in CD4<jats:sup>+<\/jats:sup> cells, may play a role in the neuropathogenesis of HTLV-1 infection.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmicb.2023.1175679","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T01:08:37Z","timestamp":1691716117000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["HTLV-1 p12 modulates the levels of prion protein (PrPC) in CD4+ T cells"],"prefix":"10.3389","volume":"14","author":[{"given":"Isabela","family":"Silva De Castro","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Granato","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael Meyer","family":"Mariante","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco Antonio","family":"Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana Claudia Celestino","family":"Leite","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ot\u00e1vio de Melo","family":"Espindola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cynthia A.","family":"Pise-Masison","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Genoveffa","family":"Franchini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rafael","family":"Linden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Juliana","family":"Echevarria-Lima","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,10]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"1331","DOI":"10.1007\/s00018-011-0879-z","article-title":"Functional mechanisms of the cellular prion protein (PrP(C)) associated anti-HIV-1 properties","volume":"69","author":"Alais","year":"2012","journal-title":"Cell. Mol. Life Sci."},{"key":"ref2","doi-asserted-by":"publisher","first-page":"9828","DOI":"10.1128\/jvi.74.21.9828-9835.2000","article-title":"Human T-lymphotropic virus type 1 open reading frame I P12(I) is required for efficient viral infectivity in primary lymphocytes","volume":"74","author":"Albrecht","year":"2000","journal-title":"J. Virol."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"3493","DOI":"10.1128\/jvi.76.7.3493-3501.2002","article-title":"Activation of nuclear factor of activated T cells by human T-lymphotropic virus type 1 accessory protein P12(I)","volume":"76","author":"Albrecht","year":"2002","journal-title":"J. Virol."},{"key":"ref4","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1006\/cimm.1999.1580","article-title":"Blood mononuclear cells in patients with HTLV-I-associated myelopathy: lymphocytes are highly activated and adhesion to endothelial cells is increased","volume":"198","author":"Al-Fahim","year":"1999","journal-title":"Cell. Immunol."},{"key":"ref5","doi-asserted-by":"publisher","first-page":"S33","DOI":"10.1097\/00042560-199600001-00007","article-title":"Tropical spastic paraparesis\/HTLV-I-associated myelopathy in Brazil","volume":"13","author":"Ara\u00fajo Ade","year":"1996","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirol."},{"key":"ref6","doi-asserted-by":"publisher","first-page":"1068","DOI":"10.1016\/S1474-4422(06)70628-7","article-title":"The HTLV-1 neurological complex","volume":"5","author":"Araujo","year":"2006","journal-title":"Lancet Neurol."},{"key":"ref7","doi-asserted-by":"publisher","first-page":"9707","DOI":"10.1128\/JVI.00887-07","article-title":"Human T-cell leukemia virus type 1 (HTLV-1) P12I down-modulates ICAM-1 and-2 and reduces adherence of natural killer cells, thereby protecting HTLV-1-infected primary CD4+ T cells from autologous natural killer cell-mediated cytotoxicity despite the reduction of major histocompatibility complex class I molecules on infected cells","volume":"81","author":"Banerjee","year":"2007","journal-title":"J. Virol."},{"key":"ref8","doi-asserted-by":"publisher","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":"Bartoe","year":"2000","journal-title":"J. Virol."},{"key":"ref9","doi-asserted-by":"publisher","first-page":"3005","DOI":"10.1073\/pnas.89.7.3005","article-title":"Expression of alternatively spliced human T-lymphotropic virus type I PX MRNA in infected cell lines and in primary uncultured cells from patients with adult T-cell leukemia\/lymphoma and healthy carriers","volume":"89","author":"Berneman","year":"1992","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"ref10","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1016\/j.ijid.2019.05.010","article-title":"Cognitive impairment in HTLV-1-associated myelopathy, proviral load and inflammatory markers","volume":"84","author":"Champs","year":"2019","journal-title":"Int. J. Infect. Dis."},{"key":"ref11","doi-asserted-by":"publisher","first-page":"1737","DOI":"10.1128\/JVI.66.3.1737-1745.1992","article-title":"Complex splicing in the human T-cell leukemia virus (HTLV) family of retroviruses: novel MRNAs and proteins produced by HTLV type I","volume":"66","author":"Ciminale","year":"1992","journal-title":"J. Virol."},{"key":"ref12","doi-asserted-by":"publisher","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":"ref13","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1007\/s00401-019-02114-9","article-title":"PrP is a central player in toxicity mediated by soluble aggregates of neurodegeneration-causing proteins","volume":"139","author":"Corbett","year":"2020","journal-title":"Acta Neuropathol."},{"key":"ref14","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1186\/1471-2334-14-453","article-title":"Human T Lymphotropic virus type 1 (HTLV-1) Proviral load induces activation of T-lymphocytes in asymptomatic carriers","volume":"14","author":"Coutinho","year":"2014","journal-title":"BMC Infect. Dis."},{"key":"ref15","doi-asserted-by":"publisher","first-page":"406","DOI":"10.3389\/fmicb.2012.00406","article-title":"HTLV tax: a fascinating multifunctional co-regulator of viral and cellular pathways","volume":"3","author":"Currer","year":"2012","journal-title":"Front. Microbiol."},{"key":"ref16","doi-asserted-by":"publisher","first-page":"10374","DOI":"10.1128\/jvi.76.20.10374-10382.2002","article-title":"Human T-cell lymphotropic virus type 1 P12(I) expression increases cytoplasmic calcium to enhance the activation of nuclear factor of activated T cells","volume":"76","author":"Ding","year":"2002","journal-title":"J. Virol."},{"key":"ref17","doi-asserted-by":"publisher","first-page":"11027","DOI":"10.1128\/jvi.77.20.11027-11039.2003","article-title":"Human T-cell lymphotropic virus type 1 P12I enhances interleukin-2 production during T-cell activation","volume":"77","author":"Ding","year":"2003","journal-title":"J. Virol."},{"key":"ref18","doi-asserted-by":"publisher","first-page":"1921","DOI":"10.1099\/vir.0.79921-0","article-title":"Tax protein of human T-cell leukaemia virus type 1 induces interleukin 17 gene expression in T cells","volume":"85","author":"Dodon","year":"2004","journal-title":"J. Gen. Virol."},{"key":"ref19","doi-asserted-by":"publisher","first-page":"e1008879","DOI":"10.1371\/journal.ppat.1008879","article-title":"Transfer of HTLV-1 P8 and gag to target T-cells depends on VASP, a novel interaction partner of P8","volume":"16","author":"Donhauser","year":"2020","journal-title":"PLoS Pathog."},{"key":"ref20","doi-asserted-by":"publisher","first-page":"488","DOI":"10.1046\/j.1365-2141.2000.01881.x","article-title":"Differential constitutive and activation-dependent expression of prion protein in human peripheral blood leucocytes","volume":"108","author":"D\u00fcrig","year":"2000","journal-title":"Br. J. Haematol."},{"key":"ref21","doi-asserted-by":"publisher","first-page":"861","DOI":"10.3390\/v3060861","article-title":"Orf-I and Orf-II-encoded proteins in HTLV-1 infection and persistence","volume":"3","author":"Edwards","year":"2011","journal-title":"Viruses"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1016\/j.rvsc.2013.06.007","article-title":"Silencing of PrP C (prion protein) expression does not affect brucella melitensis infection in human derived microglia cells","volume":"95","author":"Erdogan","year":"2013","journal-title":"Res. Vet. Sci."},{"key":"ref23","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1016\/s0306-4522(02)00155-0","article-title":"Selective expression of prion protein in peripheral tissues of the adult mouse","volume":"113","author":"Ford","year":"2002","journal-title":"Neuroscience"},{"key":"ref24","doi-asserted-by":"publisher","first-page":"8001","DOI":"10.3390\/ijms22158001","article-title":"HTLV-1 infection and pathogenesis: new insights from cellular and animal models","volume":"22","author":"Forlani","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"ref25","doi-asserted-by":"publisher","first-page":"2146","DOI":"10.3390\/v14102146","article-title":"Lessons from the cerebrospinal fluid analysis of HTLV-1-infected individuals: biomarkers of inflammation for HAM\/TSP development","volume":"14","author":"Freitas","year":"2022","journal-title":"Viruses"},{"key":"ref26","doi-asserted-by":"publisher","first-page":"9088","DOI":"10.1128\/JVI.02703-06","article-title":"Inhibition of T-cell receptor signal transduction and viral expression by the linker for activation of T cells-interacting P12(I) protein of human T-cell leukemia\/lymphoma virus type 1","volume":"81","author":"Fukumoto","year":"2007","journal-title":"J. Virol."},{"key":"ref260","doi-asserted-by":"publisher","first-page":"3726","DOI":"10.1182\/blood-2008-04-146928","volume":"113","author":"Fukumoto","year":"2009","journal-title":"\u201cIn vivo genetic mutations define predominant functions of the human T-cell leukemia\/lymphoma virus p12I protein.\u201d Blood"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"691","DOI":"10.3390\/v10120691","article-title":"Cytokine networks dysregulation during HTLV-1 infection and associated diseases","volume":"10","author":"Futsch","year":"2018","journal-title":"Viruses"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1038\/320219a0","article-title":"Origins of human T-lymphotropic viruses","volume":"320","author":"Gallo","year":"1986","journal-title":"Nature"},{"key":"ref29","doi-asserted-by":"publisher","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":"326","author":"Gessain","year":"1985","journal-title":"Lancet"},{"key":"ref30","doi-asserted-by":"publisher","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":"Gon\u00e7alves","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref31","doi-asserted-by":"publisher","first-page":"897264","DOI":"10.3389\/fmed.2022.897264","article-title":"Transient viral activation in human T cell leukemia virus type 1-infected macaques treated with Pomalidomide","volume":"9","author":"Gutowska","year":"2022","journal-title":"Front. Med."},{"key":"ref32","doi-asserted-by":"publisher","first-page":"519","DOI":"10.1002\/j.1460-2075.1988.tb02840.x","article-title":"Post-transcriptional regulator (rex) of HTLV-1 initiates expression of viral structural proteins but suppresses expression of regulatory proteins","volume":"7","author":"Hidaka","year":"1988","journal-title":"EMBO J."},{"key":"ref33","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1093\/brain\/awp298","article-title":"Pharmacological prion protein silencing accelerates central nervous system autoimmune disease via T cell receptor signalling","volume":"133","author":"Hu","year":"2010","journal-title":"Brain J. Neurol."},{"key":"ref34","first-page":"1753","article-title":"HTLV-1 rex protein accumulates unspliced RNA in the nucleus as well as in cytoplasm","volume":"6","author":"Inoue","year":"1991","journal-title":"Oncogene"},{"key":"ref35","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1111\/j.1365-2249.2006.03194.x","article-title":"The role of the cellular prion protein in the immune system","volume":"146","author":"Isaacs","year":"2006","journal-title":"Clin. Exp. Immunol."},{"key":"ref36","doi-asserted-by":"publisher","first-page":"1542","DOI":"10.1016\/j.bbamcr.2013.03.006","article-title":"CD69 overexpression by human T-cell leukemia virus type 1 tax transactivation","volume":"1833","author":"Ishikawa","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref37","doi-asserted-by":"publisher","first-page":"6086","DOI":"10.1128\/JVI.75.13.6086-6094.2001","article-title":"Free major histocompatibility complex class I heavy chain is preferentially targeted for degradation by human T-cell leukemia\/lymphotropic virus type 1 P12(I) protein","volume":"75","author":"Johnson","year":"2001","journal-title":"J. Virol."},{"key":"ref38","doi-asserted-by":"publisher","first-page":"15550","DOI":"10.1074\/jbc.M210210200","article-title":"A conserved calcineurin-binding motif in human T lymphotropic virus type 1 P12I functions to modulate nuclear factor of activated T cell activation","volume":"278","author":"Kim","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref39","doi-asserted-by":"publisher","first-page":"5463","DOI":"10.4049\/jimmunol.176.9.5463","article-title":"Enhancement of LFA-1-mediated T cell adhesion by human T lymphotropic virus type 1 P12I1","volume":"176","author":"Kim","year":"2006","journal-title":"J. Immunol."},{"key":"ref40","doi-asserted-by":"publisher","first-page":"2360","DOI":"10.1128\/JVI.67.4.2360-2366.1993","article-title":"The P12I, P13II, and P30II proteins encoded by human T-cell leukemia\/lymphotropic virus type I open reading frames I and II are localized in three different cellular compartments","volume":"67","author":"Koralnik","year":"1993","journal-title":"J. Virol."},{"key":"ref41","doi-asserted-by":"publisher","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. U. S. A."},{"key":"ref42","doi-asserted-by":"publisher","first-page":"1035","DOI":"10.1016\/j.jmb.2004.02.007","article-title":"Analysis of the interactions between HIV-1 and the cellular prion protein in a human cell line","volume":"337","author":"Leblanc","year":"2004","journal-title":"J. Mol. Biol."},{"key":"ref43","doi-asserted-by":"publisher","first-page":"877","DOI":"10.1007\/s00415-004-0455-7","article-title":"Peripheral neuropathy in HTLV-I infected individuals without tropical spastic paraparesis\/HTLV-I-associated myelopathy","volume":"251","author":"Leite","year":"2004","journal-title":"J. Neurol."},{"key":"ref44","doi-asserted-by":"publisher","first-page":"49","DOI":"10.1006\/cimm.2000.1751","article-title":"The expression and potential function of cellular prion protein in human lymphocytes","volume":"207","author":"Li","year":"2001","journal-title":"Cell. Immunol."},{"key":"ref45","doi-asserted-by":"publisher","first-page":"77","DOI":"10.3389\/fnmol.2017.00077","article-title":"The biological function of the prion protein: a cell surface scaffold of signaling modules","volume":"10","author":"Linden","year":"2017","journal-title":"Front. Mol. Neurosci."},{"key":"ref46","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1046\/j.1365-2567.1997.00331.x","article-title":"T-lymphocyte activation and the cellular form of the prion protein","volume":"92","author":"Mabbott","year":"1997","journal-title":"Immunology"},{"key":"ref47","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.1084\/jem.162.6.2169","article-title":"Origin of human T-lymphotrophic virus I-positive T cell lines in adult T cell leukemia. Analysis of T cell receptor gene rearrangement","volume":"162","author":"Maeda","year":"1985","journal-title":"J. Exp. Med."},{"key":"ref48","doi-asserted-by":"publisher","first-page":"e0179881","DOI":"10.1371\/journal.pone.0179881","article-title":"Loss of prion protein induces a primed state of type I interferon-responsive genes","volume":"12","author":"Malachin","year":"2017","journal-title":"PLoS One"},{"key":"ref49","doi-asserted-by":"publisher","first-page":"224","DOI":"10.4049\/jimmunol.1601041","article-title":"The role of shed PrPc in the neuropathogenesis of HIV infection","volume":"199","author":"Megra","year":"2017","journal-title":"J. Immunol."},{"key":"ref50","doi-asserted-by":"publisher","first-page":"e1008504","DOI":"10.1371\/journal.ppat.1008504","article-title":"The E3\/E4 ubiquitin conjugation factor UBE4B interacts with and ubiquitinates the HTLV-1 tax oncoprotein to promote NF-\u039aB activation","volume":"16","author":"Mohanty","year":"2020","journal-title":"PLoS Pathog."},{"key":"ref51","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1186\/s12977-019-0501-2","article-title":"P30 protein: a critical regulator of HTLV-1 viral latency and host immunity","volume":"16","author":"Moles","year":"2019","journal-title":"Retrovirology"},{"key":"ref52","doi-asserted-by":"publisher","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":"ref53","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1182\/blood.v98.3.823","article-title":"HTLV-1 P12(I) protein enhances STAT5 activation and decreases the Interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells","volume":"98","author":"Nicot","year":"2001","journal-title":"Blood"},{"key":"ref54","doi-asserted-by":"publisher","first-page":"1166","DOI":"10.1016\/j.imbio.2013.04.002","article-title":"Modulation of glutathione intracellular levels alters the spontaneous proliferation of lymphocyte from HTLV-1 infected patients","volume":"218","author":"Novaes","year":"2013","journal-title":"Immunobiology"},{"key":"ref55","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s12977-020-00517-1","article-title":"Functional properties and sequence variation of HTLV-1 P13","volume":"17","author":"Omsland","year":"2020","journal-title":"Retrovirology"},{"key":"ref56","doi-asserted-by":"publisher","first-page":"1031","DOI":"10.1016\/s0140-6736(86)91298-5","article-title":"HTLV-I associated myelopathy, a new clinical entity","volume":"1","author":"Osame","year":"1986","journal-title":"Lancet"},{"key":"ref57","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.jneuroim.2015.07.002","article-title":"Activation and function of murine primary microglia in the absence of the prion protein","volume":"286","author":"Pinheiro","year":"2015","journal-title":"J. Neuroimmunol."},{"key":"ref58","doi-asserted-by":"publisher","first-page":"e1004454","DOI":"10.1371\/journal.ppat.1004454","article-title":"Co-dependence of HTLV-1 P12 and P8 functions in virus persistence","volume":"10","author":"Pise-Masison","year":"2014","journal-title":"PLoS Pathog."},{"key":"ref59","doi-asserted-by":"publisher","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. U. S. A."},{"key":"ref60","doi-asserted-by":"publisher","first-page":"273","DOI":"10.1128\/cdli.1.3.273-282.1994","article-title":"Spontaneous lymphocyte proliferation in human T-cell lymphotropic virus type I (HTLV-I) and HTLV-II infection: T-cell subset responses and their relationships to the presence of provirus and viral antigen production","volume":"1","author":"Prince","year":"1994","journal-title":"Clin. Diagn. Lab. Immunol."},{"key":"ref61","doi-asserted-by":"publisher","first-page":"6058","DOI":"10.1038\/sj.onc.1208968","article-title":"Global epidemiology of HTLV-I infection and associated diseases","volume":"24","author":"Proietti","year":"2005","journal-title":"Oncogene"},{"key":"ref62","doi-asserted-by":"publisher","first-page":"333","DOI":"10.1016\/j.mam.2010.07.001","article-title":"Hijacking the T-cell communication network by the human T-cell leukemia\/lymphoma virus type 1 (HTLV-1) P12 and P8 proteins","volume":"31","author":"Prooyen","year":"2010","journal-title":"Mol. Asp. Med."},{"key":"ref63","doi-asserted-by":"publisher","first-page":"1848","DOI":"10.2353\/ajpath.2010.091006","article-title":"PrPC, the cellular isoform of the human prion protein, is a novel biomarker of HIV-associated neurocognitive impairment and mediates neuroinflammation","volume":"177","author":"Roberts","year":"2010","journal-title":"Am. J. Pathol."},{"key":"ref64","doi-asserted-by":"publisher","first-page":"106","DOI":"10.1186\/s12974-017-0879-5","article-title":"LPS-induced systemic inflammation reveals an immunomodulatory role for the prion protein at the blood-brain interface","volume":"14","author":"Salvesen","year":"2017","journal-title":"J. Neuroinflammation"},{"key":"ref65","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1186\/s12977-019-0502-1","article-title":"Role of HTLV-1 Orf-I encoded proteins in viral transmission and persistence","volume":"16","author":"Sarkis","year":"2019","journal-title":"Retrovirology"},{"key":"ref66","doi-asserted-by":"publisher","first-page":"689","DOI":"10.1086\/510679","article-title":"Human T lymphotropic virus type 1 (HTLV-1) proviral load in asymptomatic carriers, HTLV-1-associated myelopathy\/tropical spastic paraparesis, and other neurological abnormalities associated with HTLV-1 infection","volume":"44","author":"Silva","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref67","doi-asserted-by":"publisher","first-page":"737941","DOI":"10.3389\/fimmu.2021.737941","article-title":"Following the clues: usefulness of biomarkers of neuroinflammation and neurodegeneration in the investigation of HTLV-1-associated myelopathy progression","volume":"12","author":"Souza","year":"2021","journal-title":"Front. Immunol."},{"key":"ref68","doi-asserted-by":"publisher","first-page":"44604","DOI":"10.1074\/jbc.M103289200","article-title":"PrPC directly interacts with proteins involved in signaling pathways","volume":"276","author":"Spielhaupter","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref69","doi-asserted-by":"publisher","first-page":"5043","DOI":"10.1021\/bi00136a600","article-title":"Glycosylinositol phospholipid anchors of the scrapie and cellular prion proteins contain sialic acid","volume":"31","author":"Stahl","year":"1992","journal-title":"Biochemistry"},{"key":"ref70","doi-asserted-by":"publisher","first-page":"502","DOI":"10.3109\/1354750X.2015.1094141","article-title":"Immunological signature of the different clinical stages of the HTLV-1 infection: establishing serum biomarkers for HTLV-1-associated disease morbidity","volume":"20","author":"Starling","year":"2015","journal-title":"Biomarkers"},{"key":"ref71","doi-asserted-by":"publisher","first-page":"170","DOI":"10.1186\/s12974-014-0170-y","article-title":"Immune responses in rapidly progressive dementia: a comparative study of neuroinflammatory markers in Creutzfeldt-Jakob disease, Alzheimer\u2019s disease and multiple sclerosis","volume":"11","author":"Stoeck","year":"2014","journal-title":"J. Neuroinflammation"},{"key":"ref72","doi-asserted-by":"publisher","first-page":"259","DOI":"10.1155\/2001\/45454","article-title":"Human FDC express PrPc in vivo and in vitro","volume":"8","author":"Thielen","year":"2001","journal-title":"Dev. Immunol."},{"key":"ref73","doi-asserted-by":"publisher","first-page":"e36159","DOI":"10.1371\/journal.pone.0036159","article-title":"Altered prion protein expression pattern in CSF as a biomarker for Creutzfeldt-Jakob disease","volume":"7","author":"Torres","year":"2012","journal-title":"PLoS One"},{"key":"ref74","doi-asserted-by":"publisher","first-page":"1029","DOI":"10.2353\/ajpath.2008.071062","article-title":"Absence of the cellular prion protein exacerbates and prolongs neuroinflammation in experimental autoimmune encephalomyelitis","volume":"173","author":"Tsutsui","year":"2008","journal-title":"Am. J. Pathol."},{"key":"ref75","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1007\/BF01541665","article-title":"ATL and HTLV-I: in vivo cell growth of ATL cells","volume":"16","author":"Uchiyama","year":"1996","journal-title":"J. Clin. Immunol."},{"key":"ref76","doi-asserted-by":"publisher","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":"ref77","doi-asserted-by":"publisher","first-page":"3809","DOI":"10.1182\/blood-2010-05-284141","article-title":"Requirement of the human T-cell leukemia virus P12 and P30products for infectivity of human dendritic cells and macaques butnot rabbits","volume":"116","author":"Valeri","year":"2010","journal-title":"Blood"},{"key":"ref78","doi-asserted-by":"publisher","first-page":"15367","DOI":"10.1038\/s41598-021-94934-7","article-title":"Prevalence of human T-lymphotropic virus type 1 and 2 (HTLV-1\/\u22122) infection in pregnant women in Brazil: a systematic review and meta-analysis","volume":"11","author":"Vieira","year":"2021","journal-title":"Sci. Rep."},{"key":"ref79","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1016\/j.bbadis.2007.02.011","article-title":"The cellular prion protein (PrP(C)): its physiological function and role in disease","volume":"1772","author":"Westergard","year":"2007","journal-title":"Biochim. Biophys. Acta"},{"key":"ref80","doi-asserted-by":"publisher","first-page":"e12854","DOI":"10.1111\/sji.12854","article-title":"Expression and functions of cellular prion proteins in immunocytes","volume":"91","author":"Zhang","year":"2020","journal-title":"Scand. J. Immunol."}],"container-title":["Frontiers in Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1175679\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T01:08:43Z","timestamp":1691716123000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmicb.2023.1175679\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,10]]},"references-count":81,"alternative-id":["10.3389\/fmicb.2023.1175679"],"URL":"https:\/\/doi.org\/10.3389\/fmicb.2023.1175679","relation":{},"ISSN":["1664-302X"],"issn-type":[{"type":"electronic","value":"1664-302X"}],"subject":[],"published":{"date-parts":[[2023,8,10]]},"article-number":"1175679"}}