Epstein-Barr virus interferes with the amplification of IFNalpha secretion by activating suppressor of cytokine signaling 3 in primary human monocytes.
PLoS One
; 5(7): e11908, 2010 Jul 30.
Article
en En
| MEDLINE
| ID: mdl-20689596
ABSTRACT
BACKGROUND:
Epstein-Barr virus is recognized to cause lymphoproliferative disorders and is also associated with cancer. Evidence suggests that monocytes are likely to be involved in EBV pathogenesis, especially due to a number of cellular functions altered in EBV-infected monocytes, a process that may affect efficient host defense. Because type I interferons (IFNs) are crucial mediators of host defense against viruses, we investigated the effect of EBV infection on the IFNalpha pathway in primary human monocytes. METHODOLOGY/PRINCIPALFINDINGS:
Infection of monocytes with EBV induced IFNalpha secretion but inhibited the positive feedback loop for the amplification of IFNalpha. We showed that EBV infection induced the expression of suppressor of cytokine signaling 3 (SOCS3) and, to a lesser extent, SOCS1, two proteins known to interfere with the amplification of IFNalpha secretion mediated by the JAK/STAT signal transduction pathway. EBV infection correlated with a blockage in the activation of JAK/STAT pathway members and affected the level of phosphorylated IFN regulatory factor 7 (IRF7). Depletion of SOCS3, but not SOCS1, by small interfering RNA (siRNA) abrogated the inhibitory effect of EBV on JAK/STAT pathway activation and significantly restored IFNalpha secretion. Finally, transfection of monocytes with the viral protein Zta caused the upregulation of SOCS3, an event that could not be recapitulated with mutated Zta. CONCLUSIONS/SIGNIFICANCE:
We propose that EBV protein Zta activates SOCS3 protein as an immune escape mechanism that both suppresses optimal IFNalpha secretion by human monocytes and favors a state of type I IFN irresponsiveness in these cells. This immunomodulatory effect is important to better understand the aspects of the immune response to EBV.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Monocitos
/
Interferón-alfa
/
Herpesvirus Humano 4
/
Proteínas Supresoras de la Señalización de Citocinas
Límite:
Humans
Idioma:
En
Revista:
PLoS One
Asunto de la revista:
CIENCIA
/
MEDICINA
Año:
2010
Tipo del documento:
Article
País de afiliación:
Canadá