Mechanisms governing lentivirus integration site selection.

Details

Serval ID
serval:BIB_2F0DA59B4ADC
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Mechanisms governing lentivirus integration site selection.
Journal
Current Gene Therapy
Author(s)
Ciuffi A.
ISSN
1566-5232
Publication state
Published
Issued date
12/2008
Peer-reviewed
Oui
Volume
8
Number
6
Pages
419-429
Language
english
Abstract
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.
Keywords
HIV, retrovirus, lentivirus, integration site selection, mechanisms, LEDGF/p75
Pubmed
Web of science
Create date
04/02/2009 17:34
Last modification date
20/08/2019 13:13
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