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Title: Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication
Authors: Emiliani, Stéphane
Mousnier, Aurélie
Busschots, Katrien
Maroun, Marlène
Van Maele, Bénédicte
Tempé, Denis
Vandekerckhove, Linos
Moisant, Fanny
Ben-Slama, Lilia
Witvrouw, Myriam
Christ, Frauke
Rain, Jean-Christophe
Dargemont, Catherine
Debyser, Zeger
Benarous, Richard # ×
Issue Date: Jul-2005
Series Title: Journal of Biological Chemistry vol:280 issue:27 pages:25517-25523
Abstract: The insertion of a DNA copy of its RNA genome into a chromosome of the host cell is mediated by the viral integrase with the help of mostly uncharacterized cellular cofactors. We have recently described that the transcriptional co-activator LEDGF/p75 strongly interacts with HIV-1 integrase. Here we show that interaction of HIV-1 integrase with LEDGF/p75 is important for viral replication. Using multiple approaches including two-hybrid interaction studies, random and directed mutagenesis, we could demonstrate that HIV-1 virus harboring a single mutation that disrupts integrase-LEDGF/p75 interaction, resulted in defective HIV-1 replication. Furthermore, we found that LEDGF/p75 tethers HIV-1 integrase to chromosomes and that this interaction may be important for the integration process and the replication of HIV-1.
ISSN: 0021-9258
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Molecular Virology and Gene Therapy
Laboratory of Virology and Chemotherapy (Rega Institute)
× corresponding author
# (joint) last author

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