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Journal of Virology, March 2000, p. 2305-2312, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Host Sequences Flanking the Human T-Cell Leukemia Virus Type 1 Provirus In Vivo

India Leclercq,1 Franck Mortreux,1 Marielle Cavrois,1,* Arnaud Leroy,2 Antoine Gessain,3 Simon Wain-Hobson,4 and Eric Wattel5,6,*

Unité 524 INSERM, Institut de Recherche sur le Cancer de Lille,1 and Unité d'Oncogenèse Virale, Centre Oscar Lambret,2 Lille, Unité d'Epidémiologie des Virus Oncogènes,3 and Unité de Rétrovirologie Moléculaire,4 Institut Pasteur, Paris, and Unité d'Oncogenèse Virale, UMR5537 CNRS-Université Claude Bernard, Centre Léon Bérard, Lyon,5 and Service des Maladies du Sang, CHU 59037 Lille,6 France

Received 26 March 1999/Accepted 23 November 1999

Human pathogenic retroviruses do not have common loci of integration. However, many factors, such as chromatin structure, transcriptional activity, DNA-protein interaction, CpG methylation, and nucleotide composition of the target sequence, may influence integration site selection. These features have been investigated by in vitro integration reactions or by infection of cell lines with recombinant retroviruses. Less is known about target choice for integration in vivo. The present study was conducted in order to assess the characteristics of cellular sequences targeted for human T-cell leukemia virus type 1 (HTLV-1) integration in vivo. Sequencing integration sites from >= 200 proviruses (19 kb of sequence) isolated from 29 infected individuals revealed that HTLV-1 integration is not random at the level of the nucleotide sequence. The virus was found to integrate in A/T-rich regions with a weak consensus sequence at positions within and without of the hexameric repeat generated during integration. These features were not associated with a preference for integration near active regions or repeat elements of the host chromosomes. Most or all of the regions of the genome appear to be accessible to HTLV-1 integration. As with integration in vitro, integration specificity in vivo seems to be determined by local features rather than by the accessibility of specific regions.

* Corresponding author. Mailing address: Unité d'Oncogenèse Virale, UMR5537-CNRS-Université Claude Bernard, Centre Léon-Bérard, 28, rue Laënnec, 69373 Lyon Cedex 08, France. Phone: 334-78-78-26-69. Fax: 334-78-78-27-17. E-mail: ewattel{at}easynet.fr.

Journal of Virology, March 2000, p. 2305-2312, Vol. 74, No. 5
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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