Mechanisms governing lentivirus integration site selection.

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Etat: Public
Version: Final published version
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ID Serval
serval:BIB_2F0DA59B4ADC
Type
Article: article d'un périodique ou d'un magazine.
Sous-type
Synthèse (review): revue aussi complète que possible des connaissances sur un sujet, rédigée à partir de l'analyse exhaustive des travaux publiés.
Collection
Publications
Institution
Titre
Mechanisms governing lentivirus integration site selection.
Périodique
Current Gene Therapy
Auteur⸱e⸱s
Ciuffi A.
ISSN
1566-5232
Statut éditorial
Publié
Date de publication
12/2008
Peer-reviewed
Oui
Volume
8
Numéro
6
Pages
419-429
Langue
anglais
Résumé
An essential step of the life cycle of retroviruses is the stable insertion of a copy of their DNA genome into the host cell genome, and lentiviruses are no exception. This integration step, catalyzed by the viral-encoded integrase, ensures long-term expression of the viral genes, thus allowing a productive viral replication and rendering retroviral vectors also attractive for the field of gene therapy. At the same time, this ability to integrate into the host genome raises safety concerns regarding the use of retroviral-based gene therapy vectors, due to the genomic locations of integration sites. The availability of the human genome sequence made possible the analysis of the integration site preferences, which revealed to be nonrandom and retrovirus-specific, i.e. all lentiviruses studied so far favor integration in active transcription units, while other retroviruses have a different integration site distribution. Several mechanisms have been proposed that may influence integration targeting, which include (i) chromatin accessibility, (ii) cell cycle effects, and (iii) tethering proteins. Recent data provide evidence that integration site selection can occur via a tethering mechanism, through the recruitment of the lentiviral integrase by the cellular LEDGF/p75 protein, both proteins being the two major players in lentiviral integration targeting.
Mots-clé
HIV, retrovirus, lentivirus, integration site selection, mechanisms, LEDGF/p75
Pubmed
Web of science
Création de la notice
04/02/2009 17:34
Dernière modification de la notice
18/05/2023 5:54
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