Open AccessPreferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5′ Long Terminal Repeat during Oncogenesis
Author(s) -
Makito Miyazaki,
Junichirou Yasunaga,
Yuko Taniguchi,
Sadahiro Tamiya,
Tatsutoshi Nakahata,
Masao Matsuoka
Publication year - 2007
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.02511-06
Subject(s) - provirus , long terminal repeat , biology , gene , virology , human t lymphotropic virus 1 , carcinogenesis , genetics , t cell leukemia , murine leukemia virus , virus , leukemia , deltaretrovirus , microbiology and biotechnology , genome , viral disease
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 thepol andenv 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 thetax ,rex , andp30 genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. TheHTLV-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.