Preferential selection of human T-cell leukemia virus type I provirus integration sites in leukemic versus carrier states.
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 = .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.
Doi
Keitarou
K
Laboratory of Virus Immunology, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
Wu
Xiaolin
X
Taniguchi
Yuko
Y
Yasunaga
Jun-ichirou
J
Satou
Yorifumi
Y
Okayama
Akihiko
A
Nosaka
Kisato
K
Matsuoka
Masao
M
D001483:Base Sequence; D002353:Carrier State / Q000821:virology*; D002874:Chromosome Mapping; D002877:Chromosomes, Human; D015368:Human T-lymphotropic virus 1 / Q000502:physiology*; D006801:Humans; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000209:etiology / Q000821:virology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger; D012091:Repetitive Sequences, Nucleic Acid; D024363:Transcription Initiation Site; D014158:Transcription, Genetic; D016662:Virus Integration
D012333:RNA, Messenger