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J. Virol. doi:10.1128/JVI.02752-06
Copyright (c) 2007, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

HTLV-1 integration target sites in the human genome: comparison with other retroviruses

HIV Drug Resistance Program, NCI-Frederick, Frederick, Maryland 21702; Gene Expression Laboratory, AIDS Vaccine Program, Laboratory of Molecular Technology, Target Structure-Based Drug Discovery Group, SAIC-Frederick, Inc., NCI-Frederick, Frederick, Maryland 21702

^* To whom correspondence should be addressed. Email: forestwu{at}mail.nih.gov.

	Abstract

Retroviral integration into the host genome is not entirely random and integration site preference varies among different retroviruses. Human immunodeficiency virus (HIV) prefers to integrate within active genes, whereas murine leukemia virus (MLV) prefers to integrate near transcription start sites and CpG islands. On the other hand, integration of avian sarcoma-leukosis virus (ASLV) shows little preference either for genes, transcription start sites, or CpG islands. While host cellular factors play important roles in target site selection, the viral integrase is probably the major viral determinant. It is reasonable to hypothesize that retroviruses with similar integrases have similar preferences for target site selection. Although integration profiles are well defined for members of the lentivirus, spumaretrovirus, alpharetrovirus, and gammaretrovirus genera, no member of the deltaretroviruses, for example, human T cell leukemia virus type 1 (HTLV-1), have been evaluated. We have mapped 541 HTLV-1 integration sites in human HeLa cells and show that HTLV-1, like ASLV, does not specifically target transcription units and transcription start sites. Comparing the integration sites of HTLV-1 with ASLV, HIV, SIV, MLV and FV, we show that global and local integration site preferences correlate with the sequence/structure of virus-encoded integrases, supporting the idea that integrase is the major determinant of retroviral integration site selection. Our results suggest that the global integration profiles of other retroviruses could be predicted from phylogenetic comparisons of the integrase proteins. Our results show that retroviruses that engender different insertional mutagenesis risks can have similar integration profiles.

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