Integrase mutants defective for interaction with LEDGF/p75 are impaired in chromosome tethering and HIV-1 replication.
J Biol Chem
; 280(27): 25517-23, 2005 Jul 08.
Article
em En
| MEDLINE
| ID: mdl-15855167
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.
Buscar no Google
Base de dados:
MEDLINE
Assunto principal:
Infecções por HIV
/
HIV-1
/
Integrase de HIV
/
Peptídeos e Proteínas de Sinalização Intercelular
Limite:
Humans
Idioma:
En
Ano de publicação:
2005
Tipo de documento:
Article