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

doi:10.1074/jbc.M501378200

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

School of Medicine, Dentistry and Biomedical Sciences

Research output: Contribution to journal › Article › peer-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 language	English
Pages (from-to)	25517-23
Number of pages	7
Journal	The Journal of biological chemistry
Volume	280
Issue number	27
DOIs	https://doi.org/10.1074/jbc.M501378200
Publication status	Published - 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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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, J-C., Dargemont, C., Debyser, Z., & Benarous, R. (2005). Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. The Journal of biological chemistry, 280(27), 25517-23. https://doi.org/10.1074/jbc.M501378200

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. / Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication. In: The Journal of biological chemistry. 2005 ; Vol. 280, No. 27. pp. 25517-23.

@article{8946da7eab37442ca5c12f035a2b29f0,

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

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.",

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

author = "St{\'e}phane Emiliani and Aur{\'e}lie Mousnier and Katrien Busschots and Marl{\`e}ne Maroun and {Van Maele}, B{\'e}n{\'e}dicte and Denis Temp{\'e} and Linos Vandekerckhove and Fanny Moisant and Lilia Ben-Slama and Myriam Witvrouw and Frauke Christ and Jean-Christophe Rain and Catherine Dargemont and Zeger Debyser and Richard Benarous",

year = "2005",

month = jul,

day = "8",

doi = "10.1074/jbc.M501378200",

language = "English",

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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, J-C, Dargemont, C, Debyser, Z & Benarous, R 2005, 'Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication', The Journal of biological chemistry, vol. 280, no. 27, pp. 25517-23. https://doi.org/10.1074/jbc.M501378200

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

In: The Journal of biological chemistry, Vol. 280, No. 27, 08.07.2005, p. 25517-23.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication

AU - Emiliani, Stéphane

AU - Mousnier, Aurélie

AU - Busschots, Katrien

AU - Maroun, Marlène

AU - Van Maele, Bénédicte

AU - Tempé, Denis

AU - Vandekerckhove, Linos

AU - Moisant, Fanny

AU - Ben-Slama, Lilia

AU - Witvrouw, Myriam

AU - Christ, Frauke

AU - Rain, Jean-Christophe

AU - Dargemont, Catherine

AU - Debyser, Zeger

AU - Benarous, Richard

PY - 2005/7/8

Y1 - 2005/7/8

N2 - 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.

AB - 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.

KW - Chromosomes, Human

KW - Glutamine

KW - HIV Infections

KW - HIV Integrase

KW - HIV-1

KW - HeLa Cells

KW - Humans

KW - Intercellular Signaling Peptides and Proteins

KW - Virus Integration

KW - Virus Replication

U2 - 10.1074/jbc.M501378200

DO - 10.1074/jbc.M501378200

M3 - Article

C2 - 15855167

VL - 280

SP - 25517

EP - 25523

JO - Journal of Biological Chemistry

JF - Journal of Biological Chemistry

SN - 0021-9258

IS - 27

ER -