HIV blocks Type I IFN signaling through disruption of STAT1 phosphorylation.
Innate Immun
; 24(8): 490-500, 2018 11.
Article
en En
| MEDLINE
| ID: mdl-30282499
ABSTRACT
This study investigates the modulation of Type I IFN induction of an antiviral state by HIV. IFNs, including IFN-α, are key innate immune cytokines that activate the JAK/STAT pathway leading to the expression of IFN-stimulated genes. IFN-stimulated gene expression establishes the antiviral state, limiting viral infection in IFN-α-stimulated microenvironments. Our previous studies have shown that HIV proteins disrupt the induction of IFN-α by degradation of IFN-ß promoter stimulator-1, an adaptor protein for the up-regulation and release of IFN-α into the local microenvironment via the retinoic acid-inducible gene 1-like receptor signaling pathway. However, IFN-α is still released from other sources such as plasmacytoid dendritic cells via TLR-dependent recognition of HIV. Here we report that the activation of the JAK/STAT pathway by IFN-α stimulation is disrupted by HIV proteins Vpu and Nef, which both reduce IFN-α induction of STAT1 phosphorylation. Thus, HIV would still be able to avoid antiviral protection induced by IFN-α in the local microenvironment. These findings show that HIV blocks multiple signaling points that would lead to the up-regulation of IFN-stimulated genes, allowing more effective replication in IFN-α-rich environments.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
2_ODS3
Problema de salud:
2_enfermedades_transmissibles
Asunto principal:
Infecciones por VIH
/
VIH
/
Factor de Transcripción STAT1
/
Productos del Gen nef del Virus de la Inmunodeficiencia Humana
/
Proteínas del Virus de la Inmunodeficiencia Humana
/
Proteínas Reguladoras y Accesorias Virales
Límite:
Humans
Idioma:
En
Revista:
Innate Immun
Asunto de la revista:
ALERGIA E IMUNOLOGIA
/
BACTERIOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos