Quantitative phosphoproteomics reveals extensive cellular reprogramming during HIV-1 entry.
Cell Host Microbe
; 13(5): 613-623, 2013 May 15.
Article
en En
| MEDLINE
| ID: mdl-23684312
ABSTRACT
Receptor engagement by HIV-1 during host cell entry activates signaling pathways that can reprogram the cell for optimal viral replication. To obtain a global view of the signaling events induced during HIV-1 entry, we conducted a quantitative phosphoproteomics screen of primary human CD4(+) T cells after infection with an HIV-1 strain that engages the receptors CD4 and CXCR4. We quantified 1,757 phosphorylation sites with high stringency. The abundance of 239 phosphorylation sites from 175 genes, including several proteins in pathways known to be impacted by HIV-receptor binding, changed significantly within a minute after HIV-1 exposure. Several previously uncharacterized HIV-1 host factors were also identified and confirmed through RNAi depletion studies. Surprisingly, five serine/arginine-rich (SR) proteins involved in messenger RNA splicing, including the splicing factor SRm300 (SRRM2), were differentially phosophorylated. Mechanistic studies with SRRM2 suggest that HIV-1 modulates host cell alternative splicing machinery during entry in order to facilitate virus replication and release.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Fosfoproteínas
/
Linfocitos T CD4-Positivos
/
VIH-1
/
Proteoma
/
Internalización del Virus
/
Interacciones Huésped-Patógeno
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Cell Host Microbe
Asunto de la revista:
MICROBIOLOGIA
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos