Retroviral DNA integration: viral and cellular determinants of target-site selection.
Détails
Etat: Public
Version: Final published version
Licence: CC BY 4.0
ID Serval
serval:BIB_EDB114A2B2E1
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Retroviral DNA integration: viral and cellular determinants of target-site selection.
Périodique
PLoS Pathogens
ISSN
1553-7374
Statut éditorial
Publié
Date de publication
2006
Peer-reviewed
Oui
Volume
2
Numéro
6
Pages
e60
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't - old month value : Jun
Résumé
Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV) integrates preferentially within active transcription units, whereas murine leukemia virus (MLV) integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN) coding region into HIV (to make HIVmIN) caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN) further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag) displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I-hypersensitive sites (i.e., +/- 1 kb), and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins.
Mots-clé
Attachment Sites, Microbiological, Binding Sites, Chimera, Cloning, Molecular, CpG Islands, DNA, Viral, Deoxyribonuclease I, Gene Transfer Techniques, Glycosaminoglycans, HIV, Hela Cells, Humans, Integrases, Leukemia Virus, Murine, Puromycin, Retroviridae, Transcription Factors, Transcription Initiation Site, Transduction, Genetic, Virus Integration
Pubmed
Web of science
Open Access
Oui
Création de la notice
22/02/2008 15:45
Dernière modification de la notice
17/05/2023 11:29