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Integrase Mutants Defective for Interaction with LEDGF/p75 Are Impaired in Chromosome Tethering and HIV-1 Replication

Stéphane Emiliani, Aurélie Mousnier, Katrien Busschots, Marlène Maroun, Bénédicte Van Maele, Denis Tempé, Linos Vandekerckhove, Fanny Moisant, Lilia Ben-Slama, Myriam Witvrouw, Frauke Christ, Jean-Christophe Rain (+3 others)
2005 Journal of Biological Chemistry  
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
more » ... 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.
doi:10.1074/jbc.m501378200 pmid:15855167 fatcat:yxvmmse2dnh5vns2gsim3mbzxm