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.
Host sequences flanking the human T-cell leukemia virus type 1 provirus in vivo.
Résumé
en
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.
Auteur(s)
I Leclercq1, 2
, F Mortreux3
, M Cavrois4
, A Leroy5
, A Gessain6
, S Wain-Hobson7
, E Wattel3
1
CIBU -
Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats
( 31437 )
- Département Infection et Epidémiologie, 25-28 rue du Docteur Roux F-75724 Paris Cedex 15
- France
Institut Pasteur [Paris] ( 300027 )
2
UPD7 -
Université Paris Diderot - Paris 7
( 300301 )
- 5 rue Thomas-Mann - 75205 Paris cedex 13
- France
3
LBMC -
Laboratoire de Biologie Moléculaire de la Cellule
( 39378 )
- 46 allée d'Italie 69364 Lyon Cedex 07
- France
École normale supérieure de Lyon ( 6818 )
;
Université Claude Bernard Lyon 1 ( 194495 )
;
Université de Lyon ( 301088 )
;
Institut National de la Santé et de la Recherche Médicale U1210 ( 303623 )
;
Centre National de la Recherche Scientifique UMR5161 ( 441569 )
4
Génétique moléculaire et approches thérapeutiques des hémopathies malignes
( 11811 )
- IRC 1 place de Verdun 59045 Lille Cedex
- France
IRCL ( 300208 )
;
Institut National de la Santé et de la Recherche Médicale U524 ( 303623 )
5
IBMM -
Institut des Biomolécules Max Mousseron [Pôle Chimie Balard]
( 24488 )
- Faculté de Pharmacie - 15 Av. Charles Flahault - BP 14 491 - 34093 Montpellier Cedex 5
- France
Ecole Nationale Supérieure de Chimie de Montpellier ( 300370 )
;
Institut de Chimie - CNRS Chimie ( 341038 )
;
Université de Montpellier ( 410122 )
;
Centre National de la Recherche Scientifique UMR5247 ( 441569 )
6
EPVO (UMR_3569 / U-Pasteur_3) -
Epidémiologie et Physiopathologie des Virus Oncogènes
( 241105 )
- Département de Virologie, 25-28 rue du Docteur Roux F-75724 Paris Cedex 15
- France
Institut Pasteur [Paris] U-Pasteur_3 ( 300027 )
;
Université Paris Diderot - Paris 7 UMR_3569 ( 300301 )
;
Centre National de la Recherche Scientifique UMR3569 ( 441569 )
7
Rétrovirologie Moléculaire
( 35819 )
- 25-28 rue du Docteur Roux 75724 Paris Cedex 15
- France
Institut Pasteur [Paris] ( 300027 )
;
Centre National de la Recherche Scientifique URA3015 ( 441569 )
Classification
OCIS 000.1430
Page/Identifiant
2305-12
Langue du document
Anglais
Nom de la revue
Journal of Human Virology
(ISSN : 1090-9508)
Publié par Lippincott Williams & Wilkins (LWW)
Revue non référencée dans Sherpa-Romeo
Vulgarisation
Non
Comité de lecture
Oui
Audience
Internationale
Date de publication
2000-02-29
Financement
This work was supported by grants from the Association pour la Recherche sur le Cancer, from the Ligue Nationale contre le Cancer (Comité Pas de Calais), and from the Fondation Contre la Leucémie. I.L. and F.M. were supported by bursaries from the Ministère de l'Enseignement Supérieur et de la Recherche. We thank P. Wattre and collaborators, who kindly received us in their laboratories for DNA extraction, digestion, ligation, and PCR. We also thank Marie-Dominique Reynaud for assistance.
Domaine(s)
Sciences du Vivant [q-bio]/Microbiologie et Parasitologie/Virologie
Mots-clés
en
AT Rich Sequence, DNA/chemistry, DNA, Viral/genetics, HTLV-I Infections/genetics/*virology, Human T-lymphotropic virus 1/*genetics, Humans, Leukemia, T-Cell/genetics/virology, Proviruses/*genetics, Research Support, Non-U.S. Gov't, Sequence Homology, Nucleic Acid, Virus Integration
I Leclercq, F Mortreux, M Cavrois, A Leroy, A Gessain, et al.. Host sequences flanking the human T-cell leukemia virus type 1 provirus in vivo.. Journal of Human Virology, 2000, pp.2305-12. ⟨10.1128/JVI.74.5.2305-2312.2000⟩. ⟨hal-00116159⟩