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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\u2032 and 3\u2032 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\u2032 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-\u03baB 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>","DOI":"10.1128\/jvi.02511-06","type":"journal-article","created":{"date-parts":[[2007,3,8]],"date-time":"2007-03-08T03:26:05Z","timestamp":1173324365000},"page":"5714-5723","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":125,"title":["Preferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5\u2032 Long Terminal Repeat during Oncogenesis"],"prefix":"10.1128","volume":"81","author":[{"given":"Maki","family":"Miyazaki","sequence":"first","affiliation":[{"name":"Laboratory of Virus Immunology, Institute for Virus Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-Ichirou","family":"Yasunaga","sequence":"additional","affiliation":[{"name":"Laboratory of Virus Immunology, Institute for Virus Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Taniguchi","sequence":"additional","affiliation":[{"name":"Laboratory of Virus Immunology, Institute for Virus Research"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sadahiro","family":"Tamiya","sequence":"additional","affiliation":[{"name":"Department of Hematology and Department of Infectious Diseases, Graduate School of Medicine, Kumamoto University, Kumamoto 860-8556, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsutoshi","family":"Nakahata","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masao","family":"Matsuoka","sequence":"additional","affiliation":[{"name":"Laboratory of Virus Immunology, Institute for Virus Research"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.74.21.9828-9835.2000"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.66.3.396-406.2002"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0215(20000201)85:3<319::AID-IJC4>3.0.CO;2-B"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-11-4551"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0166-3542(97)00046-6"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02983553"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M307275200"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1186\/1742-4690-3-15"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1038\/307241a0"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.76.20.10374-10382.2002"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.75.16.7672-7682.2001"},{"key":"e_1_3_2_13_2","first-page":"1048","volume":"106","year":"2005","unstructured":"Doi, K., X. 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