Snapin promotes HIV-1 transmission from dendritic cells by dampening TLR8 signaling.
EMBO J
; 36(20): 2998-3011, 2017 10 16.
Article
en En
| MEDLINE
| ID: mdl-28923824
ABSTRACT
HIV-1 traffics through dendritic cells (DCs) en route to establishing a productive infection in T lymphocytes but fails to induce an innate immune response. Within DC endosomes, HIV-1 somehow evades detection by the pattern-recognition receptor (PRR) Toll-like receptor 8 (TLR8). Using a phosphoproteomic approach, we identified a robust and diverse signaling cascade triggered by HIV-1 upon entry into human DCs. A secondary siRNA screen of the identified signaling factors revealed several new mediators of HIV-1 trans-infection of CD4+ T cells in DCs, including the dynein motor protein Snapin. Inhibition of Snapin enhanced localization of HIV-1 with TLR8+ early endosomes, triggered a pro-inflammatory response, and inhibited trans-infection of CD4+ T cells. Snapin inhibited TLR8 signaling in the absence of HIV-1 and is a general regulator of endosomal maturation. Thus, we identify a new mechanism of innate immune sensing by TLR8 in DCs, which is exploited by HIV-1 to promote transmission.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Dendríticas
/
Transducción de Señal
/
VIH-1
/
Proteínas de Transporte Vesicular
/
Receptor Toll-Like 8
/
Interacciones Huésped-Patógeno
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
EMBO J
Año:
2017
Tipo del documento:
Article
País de afiliación:
Reino Unido