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Journal of Virology, June 2007, p. 5714-5723, Vol. 81, No. 11
0022-538X/07/$08.00+0 doi:10.1128/JVI.02511-06
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Laboratory of Virus Immunology, Institute for Virus Research,1 Department of Pediatrics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507,3 Department of Hematology and Department of Infectious Diseases, Graduate School of Medicine, Kumamoto University, Kumamoto 860-8556, Japan2
Received 15 November 2006/ Accepted 27 February 2007
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 pol and env 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 tax, rex, and p30 genes were frequently deleted, leaving Tax unable to activate NF-
B and CREB pathways. The HTLV-1 bZIP factor 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.
Published ahead of print on 7 March 2007.
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