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, Catherine Dargemont, Zeger Debyser, Richard Benarous

Research output: Contribution to journalArticlepeer-review

200 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)25517-23
Number of pages7
JournalThe Journal of biological chemistry
Volume280
Issue number27
DOIs
Publication statusPublished - 08 Jul 2005

Keywords

  • Chromosomes, Human
  • Glutamine
  • HIV Infections
  • HIV Integrase
  • HIV-1
  • HeLa Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Virus Integration
  • Virus Replication

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