Critical role for interferon regulatory factor 3 (IRF-3) and IRF-7 in type I interferon-mediated control of murine norovirus replication.
J Virol
; 86(24): 13515-23, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-23035219
ABSTRACT
Human noroviruses (HuNoV) are the major cause of epidemic, nonbacterial gastroenteritis in the world. The short course of HuNoV-induced symptoms has implicated innate immunity in control of norovirus (NoV) infection. Studies using murine norovirus (MNV) confirm the importance of innate immune responses during NoV infection. Type I alpha and beta interferons (IFN-α/ß) limit HuNoV replicon function, restrict MNV replication in cultured cells, and control MNV replication in vivo. Therefore, the cell types and transcription factors involved in antiviral immune responses and IFN-α/ß-mediated control of NoV infection are important to define. We used mice with floxed alleles of the IFNAR1 chain of the IFN-α/ß receptor to identify cells expressing lysozyme M or CD11c as cells that respond to IFN-α/ß to restrict MNV replication in vivo. Furthermore, we show that the transcription factors IRF-3 and IRF-7 work in concert to initiate unique and overlapping antiviral responses to restrict MNV replication in vivo. IRF-3 and IRF-7 restrict MNV replication in both cultured macrophages and dendritic cells, are required for induction of IFN-α/ß in macrophages but not dendritic cells, and are dispensable for the antiviral effects of IFN-α/ß that block MNV replication. These studies suggest that expression of the IFN-α/ß receptor on macrophages/neutrophils and dendritic cells, as well as of IRF-3 and IRF-7, is critical for innate immune responses to NoV infection.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Replicación Viral
/
Interferón Tipo I
/
Norovirus
/
Factor 3 Regulador del Interferón
/
Factor 7 Regulador del Interferón
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Virol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos