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Blood, 1 August 2005, Vol. 106, No. 3, pp. 1048-1053. Prepublished online as a Blood First Edition Paper on April 19, 2005; DOI 10.1182/blood-2004-11-4350. This Article Full Text (PDF) All Versions of this Article: 2004-11-4350v1 106/3/1048    most recent Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Doi, K. Articles by Matsuoka, M. Search for Related Content PubMed PubMed Citation Articles by Doi, K. Articles by Matsuoka, M. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 15, 2004 Accepted April 3, 2005 Preferential selection of human T-cell leukemia virus type I (HTLV-I) provirus integration sites in leukemic versus carrier states Keitarou Doi, Xiaolin Wu, Yuko Taniguchi, Jun-ichirou Yasunaga, Yorifumi Satou, Akihiko Okayama, Kisato Nosaka, and Masao Matsuoka* Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto, Japan Laboratory of Molecular Technology, National Cancer Institute-Frederick, Frederick, MD, USA Department of Laboratory Medicine, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan * Corresponding author; email: mmatsuok{at}virus.kyoto-u.ac.jp. Human T-cell leukemia virus type I (HTLV-I) is a causative agent of neoplastic disease, adult T-cell leukemia (ATL). Although the encoding viral proteins play an important role in oncogenesis, the role of the HTLV-I proviral integration site remains unsolved. We determined the integration sites of HTLV-I proviruses in ATL cells and HTLV-I-infected cells in asymptomatic carriers. In carrier and ATL cells, HTLV-I provirus was integrated into the transcriptional unit at frequencies of 26.8 (15/56) and 33.9% (20/59), respectively, which were equivalent to the frequency calculated based on random integration (33.2%). In addition, HTLV-I provirus was prone to integration near the transcriptional start sites in leukemic cells (p=0.006), and the transcriptional direction of the provirus was in accordance with that of integrated cellular genes in 70% of cases. More importantly, the integration sites in the carrier cells favored the alphoid repetitive sequences (11/56: 20%) whereas in leukemic cells they disfavored these sequences (2/59: 3.4%). Taken together, during natural course from carrier to onset of ATL, HTLV-I infected cells with integration sites favorable for viral gene transcription are susceptible to malignant transformation due to increased viral gene expression. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. Derse, B. Crise, Y. Li, G. Princler, N. Lum, C. Stewart, C. F. McGrath, S. H. Hughes, D. J. Munroe, and X. Wu Human T-Cell Leukemia Virus Type 1 Integration Target Sites in the Human Genome: Comparison with Those of Other Retroviruses J. Virol., June 15, 2007; 81(12): 6731 - 6741. [Abstract] [Full Text] [PDF] M. Miyazaki, J.-I. Yasunaga, Y. Taniguchi, S. Tamiya, T. Nakahata, and M. Matsuoka Preferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5' Long Terminal Repeat during Oncogenesis J. Virol., June 1, 2007; 81(11): 5714 - 5723. [Abstract] [Full Text] [PDF]

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