Gamma interferon (IFN-γ) receptor restricts systemic dengue virus replication and prevents paralysis in IFN-α/ß receptor-deficient mice.
J Virol
; 86(23): 12561-70, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22973027
ABSTRACT
We previously reported that mice lacking alpha/beta and gamma interferon receptors (IFN-α/ßR and -γR) uniformly exhibit paralysis following infection with the dengue virus (DENV) clinical isolate PL046, while only a subset of mice lacking the IFN-γR alone and virtually no mice lacking the IFN-α/ßR alone develop paralysis. Here, using a mouse-passaged variant of PL046, strain S221, we show that in the absence of the IFN-α/ßR, signaling through the IFN-γR confers approximately 140-fold greater resistance against systemic vascular leakage-associated dengue disease and virtually complete protection from dengue-induced paralysis. Viral replication in the spleen was assessed by immunohistochemistry and flow cytometry, which revealed a reduction in the number of infected cells due to IFN-γR signaling by 2 days after infection, coincident with elevated levels of IFN-γ in the spleen and serum. By 4 days after infection, IFN-γR signaling was found to restrict DENV replication systemically. Clearance of DENV, on the other hand, occurred in the absence of IFN-γR, except in the central nervous system (CNS) (brain and spinal cord), where clearance relied on IFN-γ from CD8(+) T cells. These results demonstrate the roles of IFN-γR signaling in protection from initial systemic and subsequent CNS disease following DENV infection and demonstrate the importance of CD8(+) T cells in preventing DENV-induced CNS disease.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Parálisis
/
Replicación Viral
/
Sistema Nervioso Central
/
Receptores de Interferón
/
Dengue
/
Virus del Dengue
/
Susceptibilidad a Enfermedades
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
Límite:
Animals
Idioma:
En
Revista:
J Virol
Año:
2012
Tipo del documento:
Article
País de afiliación:
Estados Unidos