The Lentiviral Integrase Binding Protein LEDGF/p75 and HIV-1 Replication

The Lentiviral Integrase Binding Protein LEDGF/p75 and HIV-1 Replication

DSpace/Manakin Repository

The Lentiviral Integrase Binding Protein LEDGF/p75 and HIV-1 Replication

dc.contributor.author	Cherepanov, Peter
dc.contributor.author	Engelman, Alan N.
dc.date.accessioned	2010-12-08T17:59:58Z
dc.date.issued	2008
dc.identifier.citation	Engelman, Alan, and Peter Cherepanov. 2008. The lentiviral integrase binding protein LEDGF/p75 and HIV-1 replication. PLoS Pathogens 4(3): e1000046.	en_US
dc.identifier.issn	1553-7366	en_US
dc.identifier.uri	http://nrs.harvard.edu/urn-3:HUL.InstRepos:4621013
dc.description.abstract	Retroviral replication proceeds through a stable proviral DNA intermediate, and numerous host cell factors have been implicated in its formation. In particular, recent results have highlighted an important role for the integrase-interactor lens epithelium-derived growth factor (LEDGF)/p75 in lentiviral integration. Cells engineered to over-express fragments of LEDGF/p75 containing its integrase-binding domain but lacking determinants essential for chromatin association are refractory to HIV-1 infection. Furthermore, both the levels of HIV-1 integration and the genomic distribution of the resultant proviruses are significantly perturbed in cells devoid of endogenous LEDGF/p75 protein. A strong bias towards integration along transcription units is a characteristic feature of lentiviruses. In the absence of LEDGF/p75, HIV-1 in large part loses that preference, displaying concomitant integration surges in the vicinities of CpG islands and gene promoter regions, elements naturally targeted by other types of retroviruses. Together, these findings highlight that LEDGF/p75 is an important albeit not strictly essential cofactor of lentiviral DNA integration, and solidify a role for chromatin-associated LEDGF/p75 as a receptor for lentiviral preintegration complexes. By now one of the best characterized virus–host interactions, the integrase-LEDGF/p75 interface opens a range of opportunities for lentiviral vector targeting for gene therapy applications as well as for the development of novel classes of antiretroviral drugs.	en_US
dc.language.iso	en_US	en_US
dc.publisher	Public Library of Science	en_US
dc.relation.isversionof	doi:10.1371/journal.ppat.1000046	en_US
dc.relation.hasversion	http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2275779/pdf/	en_US
dash.license	LAA
dc.subject	virology	en_US
dc.subject	viral replication and gene regulation	en_US
dc.subject	immunodeficiency viruses	en_US
dc.title	The Lentiviral Integrase Binding Protein LEDGF/p75 and HIV-1 Replication	en_US
dc.type	Journal Article	en_US
dc.description.version	Version of Record	en_US
dc.relation.journal	PLoS Pathogens	en_US
dash.depositing.author	Engelman, Alan N.
dc.date.available	2010-12-08T17:59:58Z
dash.affiliation.other	HMS^Medicine- Beth Israel-Deaconess	en_US