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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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