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

(2005) JOURNAL OF BIOLOGICAL CHEMISTRY. 280(27). p.25517-25523
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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 integraseLEDGF/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.
Keywords
ACUTE INFECTION, EARLY STEPS, NUCLEAR-LOCALIZATION, IN-VITRO, HUMAN-CELLS, HUMAN GENOME, CDNA INTEGRATION, DNA INTEGRATION, PREINTEGRATION COMPLEXES, IMMUNODEFICIENCY-VIRUS TYPE-1

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Citation

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Chicago
Emiliani, Stéphane, Aurélie Mousnier, Katrien Busschots, Marlène Maroun, Bénédicte Van Maele, Denis Tempe, Linos Vandekerckhove, et al. 2005. “Integrase Mutants Defective for Interaction with LEDGF/p75 Are Impaired in Chromosome Tethering and HIV-1 Replication.” Journal of Biological Chemistry 280 (27): 25517–25523.
APA
Emiliani, S., Mousnier, A., Busschots, K., Maroun, M., Van Maele, B., Tempe, D., Vandekerckhove, L., et al. (2005). Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. JOURNAL OF BIOLOGICAL CHEMISTRY, 280(27), 25517–25523.
Vancouver
1.
Emiliani S, Mousnier A, Busschots K, Maroun M, Van Maele B, Tempe D, et al. Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. JOURNAL OF BIOLOGICAL CHEMISTRY. 2005;280(27):25517–23.
MLA
Emiliani, Stéphane, Aurélie Mousnier, Katrien Busschots, et al. “Integrase Mutants Defective for Interaction with LEDGF/p75 Are Impaired in Chromosome Tethering and HIV-1 Replication.” JOURNAL OF BIOLOGICAL CHEMISTRY 280.27 (2005): 25517–25523. Print.
@article{1206480,
  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 integraseLEDGF/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.},
  author       = {Emiliani, St{\'e}phane and Mousnier, Aur{\'e}lie and Busschots, Katrien and Maroun, Marl{\`e}ne and Van Maele, B{\'e}n{\'e}dicte and Tempe, Denis and Vandekerckhove, Linos and Moisant, Fanny and Ben-Slama, Lilia and Witvrouw, Myriam and Christ, Frauke and Rain, Jean-Christophe and Dargemont, Catherine and Debyser, Zeger and Benarous, Richard},
  issn         = {0021-9258},
  journal      = {JOURNAL OF BIOLOGICAL CHEMISTRY},
  keyword      = {ACUTE INFECTION,EARLY STEPS,NUCLEAR-LOCALIZATION,IN-VITRO,HUMAN-CELLS,HUMAN GENOME,CDNA INTEGRATION,DNA INTEGRATION,PREINTEGRATION COMPLEXES,IMMUNODEFICIENCY-VIRUS TYPE-1},
  language     = {eng},
  number       = {27},
  pages        = {25517--25523},
  title        = {Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication},
  volume       = {280},
  year         = {2005},
}

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