{"doi":"10.1128/jvi.02511-06","title":"Preferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5′ Long Terminal Repeat during Oncogenesis","abstract":"<jats:title>ABSTRACT</jats:title><jats:p>In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5′ long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 proviruses retaining both LTRs, 6-bp repeat sequences were adjacent to the 5′ and 3′ LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of the<jats:italic>pol</jats:italic>and<jats:italic>env</jats:italic>genes at the 5′ end, suggesting that these type 2 defective proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26-bp) deletions in the host genome were identified, indicating that these defective proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective proviruses, the second exons of the<jats:italic>tax</jats:italic>,<jats:italic>rex</jats:italic>, and<jats:italic>p30</jats:italic>genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. The<jats:italic>HTLV-1 bZIP factor</jats:italic>gene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis.</jats:p>","journal":"Journal of 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Tamiya","orcid":null,"position":3,"is_corresponding":false},{"id":116908,"name":"Tatsutoshi Nakahata","orcid":null,"position":4,"is_corresponding":false},{"id":116909,"name":"Masao Matsuoka","orcid":null,"position":5,"is_corresponding":false},{"id":116904,"name":"Maki Miyazaki","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"base_score":4.919980925828125,"endowment":4.919980925828125,"datacite_reuse_total":14,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"17344291","pmcid":"PMC1900290","openalex_id":"https://openalex.org/W1997923723","authors":[],"funders":[],"total_grants":0,"fwci":2.3382,"citation_percentile":0.88775137,"influential_citations":7,"citation_trend":[{"year":2012,"count":3},{"year":2013,"count":7},{"year":2014,"count":5},{"year":2015,"count":6},{"year":2016,"count":8},{"year":2017,"count":8},{"year":2018,"count":3},{"year":2019,"count":7},{"year":2020,"count":5},{"year":2021,"count":16},{"year":2022,"count":18},{"year":2023,"count":5},{"year":2024,"count":3},{"year":2025,"count":9},{"year":2026,"count":4}],"oa_status":"green","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1900290","host_type":"repository"},{"url":"https://doi.org/10.1128/jvi.02511-06","host_type":"GREEN"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/1900290","host_type":"repository"},{"url":"https://journals.asm.org/doi/pdf/10.1128/JVI.02511-06","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/17344291","host_type":"repository"}],"fields_of_study":["T-cell and Retrovirus Studies","Vector-Borne Animal Diseases","Animal Disease Management and Epidemiology","Biology","Medicine","Amino Acid Sequence","Base Sequence","Basic-Leucine Zipper Transcription Factors","Cell Line, Tumor","Human T-lymphotropic virus 1","Humans","Leukemia-Lymphoma, Adult T-Cell","Molecular Sequence Data","Proviruses","Retroviridae Proteins","Terminal Repeat Sequences","Viral Proteins","Virus Integration"],"mesh_terms":["Amino Acid Sequence","Base Sequence","Humans","Molecular Sequence Data","Proviruses","Retroviridae Proteins","Viral Proteins","Human T-lymphotropic virus 1","Leukemia-Lymphoma, Adult T-Cell","Virus Integration","Terminal Repeat Sequences","Cell Line, Tumor","Basic-Leucine Zipper Transcription Factors"],"keywords":["Provirus","Long terminal repeat","Biology","Gene","Virology","Human T-lymphotropic virus 1","Carcinogenesis","Genetics","T-cell leukemia","Murine leukemia virus","Virus","Leukemia","Deltaretrovirus","Molecular biology","Genome","Viral 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