Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication.
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.
Emiliani
Stéphane
S
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.
Mousnier
Aurélie
A
Busschots
Katrien
K
Maroun
Marlène
M
Van Maele
Bénédicte
B
Tempé
Denis
D
Vandekerckhove
Linos
L
Moisant
Fanny
F
Ben-Slama
Lilia
L
Witvrouw
Myriam
M
Christ
Frauke
F
Rain
Jean-Christophe
JC
Dargemont
Catherine
C
Debyser
Zeger
Z
Benarous
Richard
R
D002877:Chromosomes, Human / Q000821:virology; D005973:Glutamine / Q000378:metabolism; D015658:HIV Infections / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D019427:HIV Integrase / Q000235:genetics* / Q000378:metabolism*; D015497:HIV-1 / Q000235:genetics / Q000254:growth & development*; D006367:HeLa Cells; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism*; D016662:Virus Integration / Q000502:physiology; D014779:Virus Replication / Q000502:physiology
D036341:Intercellular Signaling Peptides and Proteins; C119380:lens epithelium-derived growth factor; D005973:Glutamine; D019427:HIV Integrase