{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:15:51Z","timestamp":1791404151545,"version":"4.3.3"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T00:00:00Z","timestamp":1457913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"publisher","award":["092430\/Z\/10\/Z"],"award-info":[{"award-number":["092430\/Z\/10\/Z"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000651","name":"Leukaemia and Lymphoma Research","doi-asserted-by":"publisher","award":["LLR 12041"],"award-info":[{"award-number":["LLR 12041"]}],"id":[{"id":"10.13039\/501100000651","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000651","name":"Leukaemia and Lymphoma Research","doi-asserted-by":"publisher","award":["LLR 09006"],"award-info":[{"award-number":["LLR 09006"]}],"id":[{"id":"10.13039\/501100000651","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Clonal expansion of human T-lymphotropic virus type-1 (HTLV-1) infected cells in vivo is well documented. Unlike human immunodeficiency virus type 1 (HIV-1), HTLV-1 plasma RNA is sparse. The contribution of the \u201cmitotic\u201d spread of HTLV-1 compared with infectious spread of the virus to HTLV-1 viral burden in established infection is uncertain. Since extrachromosomal long terminal repeat (LTR) DNA circles are indicators of viral replication in HIV-1 carriers with undetectable plasma HIV RNA, we hypothesised that HTLV-1 LTR circles could indicate reverse transcriptase (RT) usage and infectious activity. 1LTR and 2LTR DNA circles were measured in HTLV-1 cell lines and peripheral blood mononuclear cells (PBMC) of asymptomatic carriers (ACs) and patients with HTLV-1-associated myelopathy\/tropical spastic paraparesis (HAM\/TSP) or adult T cell leukaemia\/lymphoma (ATLL). 1LTR DNA circles were detected in 14\/20 patients at a mean of 1.38\/100 PBMC but did not differentiate disease status nor correlate with HTLV-1 DNA copies. 2LTR DNA circles were detected in 30\/31 patients and at higher concentrations in patients with HTLV-1-associated diseases, independent of HTLV-1 DNA load. In an incident case the 2LTR DNA circle concentration increased 2.1 fold at the onset of HAM\/TSP compared to baseline. Detectable and fluctuating levels of HTLV-1 DNA circles in patients indicate viral RT usage and virus replication. Our results indicate HTLV-1 viral replication capacity is maintained in chronic infection and may be associated with disease onset.<\/jats:p>","DOI":"10.3390\/v8030080","type":"journal-article","created":{"date-parts":[[2016,3,14]],"date-time":"2016-03-14T11:03:45Z","timestamp":1457953425000},"page":"80","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Long Terminal Repeat Circular DNA as Markers of Active Viral Replication of Human T Lymphotropic Virus-1 in Vivo"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-7029","authenticated-orcid":false,"given":"James","family":"Fox","sequence":"first","affiliation":[{"name":"Centre for Immunology and Infection, Department of Biology &amp; Hull York Medical School, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silva","family":"Hilburn","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Imperial College, London W2 1PG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria-Antonietta","family":"Demontis","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Imperial College, London W2 1PG, UK"},{"name":"The National Centre for Human Retrovirology\/HTLV Clinic, Imperial College Healthcare NHS Trust, St Mary\u2019s Hospital, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Brighty","sequence":"additional","affiliation":[{"name":"Division of Cancer Research, Ninewells Hospital &amp; Medical School, University of Dundee, Dundee DD1 9SY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rios Grassi","sequence":"additional","affiliation":[{"name":"Oswaldo Cruz Foundation, Gon\u00e7alo Moniz Research Center-BA, Advanced Laboratory of Public Health, Salvador, Bahia, Candeal 40296-710, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernardo","family":"Galv\u00e3o-Castro","sequence":"additional","affiliation":[{"name":"HTLV-Centre Bahian School of Medicine, Salvador, Bahia 40050-420, Brazil"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3773-2390","authenticated-orcid":false,"given":"Graham","family":"Taylor","sequence":"additional","affiliation":[{"name":"Section of Infectious Diseases, Department of Medicine, Imperial College, London W2 1PG, UK"},{"name":"The National Centre for Human Retrovirology\/HTLV Clinic, Imperial College Healthcare NHS Trust, St Mary\u2019s Hospital, London W2 1NY, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabiola","family":"Martin","sequence":"additional","affiliation":[{"name":"Centre for Immunology and Infection, Department of Biology &amp; Hull York Medical School, University of York, York YO10 5DD, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2016,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"6476","DOI":"10.1073\/pnas.78.10.6476","article-title":"Adult T-cell leukemia: antigen in an ATL cell line and detection of antibodies to the antigen in human sera","volume":"78","author":"Hinuma","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"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":"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":"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":"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_6","doi-asserted-by":"crossref","first-page":"2525","DOI":"10.1073\/pnas.86.8.2525","article-title":"Retroviral integration: structure of the initial covalent product and its precursor, and a role for the viral IN protein","volume":"86","author":"Brown","year":"1989","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1383","DOI":"10.1016\/0092-8674(78)90063-6","article-title":"Mapping unintegrated avian sarcoma virus DNA: termini of linear DNA bear 300 nucleotides present once or twice in two species of circular DNA","volume":"15","author":"Shank","year":"1978","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1038\/255646a0","article-title":"Partially single-stranded form of free Moloney viral DNA","volume":"255","author":"Gianni","year":"1975","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1128\/jvi.33.1.377-389.1980","article-title":"Structure of murine sarcoma virus DNA replicative intermediates synthesized in vitro","volume":"33","author":"Dina","year":"1980","journal-title":"J. Virol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1016\/0092-8674(79)90101-6","article-title":"In vitro synthesis of a 9 kbp terminally redundant DNA carrying the infectivity of Moloney murine leukemia virus","volume":"16","author":"Gilboa","year":"1979","journal-title":"Cell"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1073\/pnas.78.1.124","article-title":"Nucleotide sequence of cloned unintegrated avian sarcoma virus DNA: viral DNA contains direct and inverted repeats similar to those in transposable elements","volume":"78","author":"Swanstrom","year":"1981","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1128\/jvi.42.1.346-351.1982","article-title":"Restriction endonuclease and nucleotide sequence analyses of molecularly cloned unintegrated avian tumor virus DNA: structure of large terminal repeats in circle junctions","volume":"42","author":"Katz","year":"1982","journal-title":"J. Virol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"6942","DOI":"10.1128\/jvi.65.12.6942-6952.1991","article-title":"Circularization of human immunodeficiency virus type 1 DNA in vitro","volume":"65","author":"Farnet","year":"1991","journal-title":"J. Virol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1035","DOI":"10.1084\/jem.172.4.1035","article-title":"Reinfection results in accumulation of unintegrated viral DNA in cytopathic and persistent human immunodeficiency virus type 1 infection of CEM cells","volume":"172","author":"Pauza","year":"1990","journal-title":"J. Exp. Med."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"4836","DOI":"10.1128\/jvi.64.10.4836-4841.1990","article-title":"Accumulation of human immunodeficiency virus type 1 DNA in T cells: results of multiple infection events","volume":"64","author":"Robinson","year":"1990","journal-title":"J. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/387183a0","article-title":"Quantification of latent tissue reservoirs and total body viral load in HIV-1 infection","volume":"387","author":"Chun","year":"1997","journal-title":"Nature"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1038\/71569","article-title":"Persistence of episomal HIV-1 infection intermediates in patients on highly active anti-retroviral therapy","volume":"6","author":"Sharkey","year":"2000","journal-title":"Nat. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1016\/S0092-8674(00)80828-4","article-title":"HIV-1 genome nuclear import is mediated by a central DNA flap","volume":"101","author":"Zennou","year":"2000","journal-title":"Cell"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/nm.2111","article-title":"HIV-1 replication and immune dynamics are affected by raltegravir intensification of HAART-suppressed subjects","volume":"16","author":"Buzon","year":"2010","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3603","DOI":"10.3390\/v7072793","article-title":"Modes of Human T Cell Leukemia Virus Type 1 Transmission, Replication and Persistence","volume":"7","author":"Carpentier","year":"2015","journal-title":"Viruses"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Martin, J.L., Maldonado, J.O., Mueller, J.D., Zhang, W., and Mansky, L.M. (2016). Molecular Studies of HTLV-1 Replication: An Update. Viruses, 8.","DOI":"10.3390\/v8020031"},{"key":"ref_22","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_23","first-page":"270","article-title":"Human T-cell leukaemia virus type 1 (HTLV-1) infectivity and cellular transformation. Nature reviews","volume":"7","author":"Matsuoka","year":"2007","journal-title":"Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"10580","DOI":"10.1128\/JVI.01799-15","article-title":"Viral Source-Independent High Susceptibility of Dendritic Cells to Human T-Cell Leukemia Virus Type 1 Infection Compared to That of T Lymphocytes","volume":"89","author":"Alais","year":"2015","journal-title":"J. Virol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"2130","DOI":"10.1002\/jmv.24264","article-title":"HTLV-1 viral RNA is detected rarely in plasma of HTLV-1 infected subjects","volume":"87","author":"Demontis","year":"2015","journal-title":"J Med Virol"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1097\/00042560-199605010-00001","article-title":"Examining the molecular genetics of HTLV-I with an infectious molecular clone of the virus and permissive cell culture systems","volume":"12","author":"Derse","year":"1996","journal-title":"J. Acquir. Immune Defic. Syndr. Hum. Retrovirol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1135","DOI":"10.1089\/aid.1994.10.1135","article-title":"Familial transmission and minimal sequence variability of human T-lymphotropic virus type I (HTLV-I) in Zaire","volume":"10","author":"Liu","year":"1994","journal-title":"AIDS Res. Hum. Retroviruses."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s12977-015-0236-7","article-title":"Rapid dissemination of human T-lymphotropic virus type 1 during primary infection in transplant recipients","volume":"13","author":"Cook","year":"2016","journal-title":"Retrovirology"},{"key":"ref_29","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. Retrovir."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"424","DOI":"10.1086\/376531","article-title":"Susceptibility of human T cell leukemia virus type I to nucleoside reverse transcriptase inhibitors","volume":"188","author":"Hill","year":"2003","journal-title":"J. Infect. Dis."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2852","DOI":"10.2741\/1442","article-title":"Adult T cell leukemia lymphoma","volume":"9","author":"Ratner","year":"2004","journal-title":"Front. Biosci."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"469","DOI":"10.3390\/v3050469","article-title":"Susceptibility of primary HTLV-1 isolates from patients with HTLV-1-associated myelopathy to reverse transcriptase inhibitors","volume":"3","author":"Macchi","year":"2011","journal-title":"Viruses"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1093\/jac\/dkr404","article-title":"Antiviral effect of raltegravir on HTLV-1 carriers","volume":"67","author":"Trevino","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1046\/j.1365-2141.2001.02794.x","article-title":"Interferon alpha and zidovudine therapy in adult T-cell leukaemia lymphoma: response and outcome in 15 patients","volume":"113","author":"Matutes","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1186\/1742-4690-3-63","article-title":"Zidovudine plus lamivudine in Human T-Lymphotropic Virus type-I-associated myelopathy: a randomised trial","volume":"3","author":"Taylor","year":"2006","journal-title":"Retrovirology"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3802","DOI":"10.1182\/blood-2010-02-270751","article-title":"Highly active antiretroviral treatment against STLV-1 infection combining reverse transcriptase and HDAC inhibitors","volume":"116","author":"Afonso","year":"2010","journal-title":"Blood"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1182\/blood-2008-03-136770","article-title":"HTLV-1-Tax and ICAM-1 act on T-cell signal pathways to polarize the microtubule-organizing center at the virological synapse","volume":"114","author":"Nejmeddine","year":"2009","journal-title":"Blood"},{"key":"ref_38","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","volume":"299","author":"Igakura","year":"2003","journal-title":"Science"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"29653","DOI":"10.1074\/jbc.M502639200","article-title":"Human T-lymphotropic virus, type 1, tax protein triggers microtubule reorientation in the virological synapse","volume":"280","author":"Nejmeddine","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Majorovits, E., Nejmeddine, M., Tanaka, Y., Taylor, G.P., Fuller, S.D., and Bangham, C.R. (2008). Human T-lymphotropic virus-1 visualized at the virological synapse by electron tomography. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0002251"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/nm.2065","article-title":"Biofilm-like extracellular viral assemblies mediate HTLV-1 cell-to-cell transmission at virological synapses","volume":"16","author":"Sachse","year":"2010","journal-title":"Nat. Med."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1106","DOI":"10.1126\/science.1059128","article-title":"Selection forces and constraints on retroviral sequence variation","volume":"292","author":"Overbaugh","year":"2001","journal-title":"Science"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0166-0934(98)00093-7","article-title":"Quantification of proviral DNA load in human T-cell leukaemia virus type I infections","volume":"75","author":"Tosswill","year":"1998","journal-title":"J. Virol. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/bioinformatics\/btm091","article-title":"Enhancements and modifications of primer design program Primer3","volume":"23","author":"Koressaar","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e115","DOI":"10.1093\/nar\/gks596","article-title":"Primer3 - new capabilities and interfaces","volume":"40","author":"Untergasser","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"3335","DOI":"10.1182\/blood.V99.9.3335","article-title":"High frequencies of Th1-type CD4(+) T cells specific to HTLV-1 Env and Tax proteins in patients with HTLV-1-associated myelopathy\/tropical spastic paraparesis","volume":"99","author":"Goon","year":"2002","journal-title":"Blood"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"3281","DOI":"10.1128\/JVI.77.5.3281-3290.2003","article-title":"An antiviral peptide targets a coiled-coil domain of the human T-cell leukemia virus envelope glycoprotein","volume":"77","author":"Pinon","year":"2003","journal-title":"J. Virol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"A51","DOI":"10.1186\/1742-4690-8-S1-A51","article-title":"Circularised 1 and 2 LTR DNA circles are present in freshly- and chronically-infected cell lines and patient PBMCs, indicating ongoing reverse transcriptase usage","volume":"8","author":"Fox","year":"2011","journal-title":"Retrovirology"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/0042-6822(83)90395-1","article-title":"Restricted expression of human T-cell leukemia--lymphoma virus (HTLV) in transformed human umbilical cord blood lymphocytes","volume":"129","author":"Salahuddin","year":"1983","journal-title":"Virology"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1126\/science.2992081","article-title":"Infection of HTLV-III\/LAV in HTLV-I-carrying cells MT-2 and MT-4 and application in a plaque assay","volume":"229","author":"Harada","year":"1985","journal-title":"Science"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1336","DOI":"10.1136\/jnnp.2009.191239","article-title":"A 15-year prospective longitudinal study of disease progression in patients with HTLV-1 associated myelopathy in the UK","volume":"81","author":"Martin","year":"2010","journal-title":"J. Neurol. Neurosurg. Psychiatry"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"651","DOI":"10.1099\/0022-1317-69-3-651","article-title":"Epigenetic control and reintegration of extrachromosomal proviral DNA in HL60 cells chronically infected with human T cell leukaemia virus type 1","volume":"69 (Pt 3)","author":"Hiramatsu","year":"1988","journal-title":"J. Gen. Virol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1089\/aid.1993.9.1167","article-title":"Unintegrated two-long terminal repeat circular human T lymphotropic virus DNA accumulation during chronic HTLV infection","volume":"9","author":"Kitamura","year":"1993","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1016\/j.jviromet.2006.07.022","article-title":"PCR-based detection is unable to consistently distinguish HIV 1LTR circles","volume":"138","author":"Yoder","year":"2006","journal-title":"J. Virol. Methods"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1699","DOI":"10.1089\/aid.1992.8.1699","article-title":"Dendritic cells from patients with tropical spastic paraparesis are infected with HTLV-1 and stimulate autologous lymphocyte proliferation","volume":"8","author":"Macatonia","year":"1992","journal-title":"AIDS Res. Hum. Retrovir."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/j.1365-2141.2004.04956.x","article-title":"Depletion and impaired interferon-alpha-producing capacity of blood plasmacytoid dendritic cells in human T-cell leukaemia virus type I-infected individuals","volume":"125","author":"Hishizawa","year":"2004","journal-title":"Br. J. Haematol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3700","DOI":"10.1128\/jvi.63.9.3700-3707.1989","article-title":"Persistent human immunodeficiency virus type 1 infection of monoblastoid cells leads to accumulation of self-integrated viral DNA and to production of defective virions","volume":"63","author":"Pauza","year":"1989","journal-title":"J. Virol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5723","DOI":"10.4049\/jimmunol.0900069","article-title":"The avidity and lytic efficiency of the CTL response to HTLV-1","volume":"182","author":"Kattan","year":"2009","journal-title":"J. Immunol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"10376","DOI":"10.1128\/JVI.77.19.10376-10382.2003","article-title":"Early transcription from nonintegrated DNA in human immunodeficiency virus infection","volume":"77","author":"Wu","year":"2003","journal-title":"J. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1023","DOI":"10.1016\/S1286-4579(03)00187-4","article-title":"Gene transcription in HIV infection","volume":"5","author":"Wu","year":"2003","journal-title":"Microbes Infect."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1503","DOI":"10.1126\/science.1061548","article-title":"Selective transcription and modulation of resting T cell activity by preintegrated HIV DNA","volume":"293","author":"Wu","year":"2001","journal-title":"Science"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"3962","DOI":"10.1128\/JVI.77.7.3962-3972.2003","article-title":"Human immunodeficiency virus type 1 (HIV-1) Vpr enhances expression from unintegrated HIV-1 DNA","volume":"77","author":"Poon","year":"2003","journal-title":"J. Virol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"9753","DOI":"10.1128\/JVI.75.20.9753-9761.2001","article-title":"Infection of lymphoid cells by integration-defective human immunodeficiency virus type 1 increases de novo methylation","volume":"75","author":"Fang","year":"2001","journal-title":"J. Virol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"5393","DOI":"10.1074\/jbc.271.10.5393","article-title":"HIV-1 protein expression from synthetic circles of DNA mimicking the extrachromosomal forms of viral DNA","volume":"271","author":"Cara","year":"1996","journal-title":"J. Biol. Chem."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/8\/3\/80\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T19:20:41Z","timestamp":1760210441000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/8\/3\/80"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,3,14]]},"references-count":64,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2016,3]]}},"alternative-id":["v8030080"],"URL":"https:\/\/doi.org\/10.3390\/v8030080","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,3,14]]}}}