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    J Biol Chem. 2005 Jul 8;280(27):25517-23. Epub 2005 Apr 25.

    Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication.

    Emiliani S, Mousnier A, Busschots K, Maroun M, Van Maele B, Tempé D, Vandekerckhove L, Moisant F, Ben-Slama L, Witvrouw M, Christ F, Rain JC, Dargemont C, Debyser Z, Benarous R.

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    Institut Cochin, U567 INSERM, UPR8104 CNRS, Université Paris VI et VII, Tour 43, 2e étage, couloir 43-44, 2 place Jussieu, F-75251 Paris cedex 05, France.

    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.

    PMID:
    15855167
    [PubMed - indexed for MEDLINE]
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