STAT1-independent control of a neurotropic measles virus challenge in primary neurons and infected mice.
J Immunol
; 188(4): 1915-23, 2012 Feb 15.
Article
em En
| MEDLINE
| ID: mdl-22246627
ABSTRACT
Neurons are chiefly nonrenewable; thus, cytolytic immune strategies to clear or control neurotropic viral infections could have lasting neurologic consequences. IFN-γ is a potent antiviral cytokine that is critical for noncytolytic clearance of multiple neurotropic viral infections, including measles virus (MV); however, the downstream pathways through which IFN-γ functions in neurons have not been defined. Unlike most cell types studied to date in which IFN-γ affects gene expression via rapid and robust activation of STAT1, basal STAT1 levels in primary hippocampal neurons are constitutively low, resulting in attenuated STAT1 activation and consequently slower kinetics of IFN-γ-driven STAT1-dependent gene expression. Given this altered expression and activation of STAT1 in neurons, we sought to determine whether STAT1 was required for IFN-γ-mediated protection from infection in neurons. To do so, we evaluated the consequences of MV challenge of STAT1-deficient mice and primary hippocampal neurons explanted from these mice. Surprisingly, the absence of STAT1 did not restrict the ability of IFN-γ to control viral infection either in vivo or ex vivo. Moreover, the canonical IFN-γ-triggered STAT1 gene expression profile was not induced in STAT1-deficient neurons, suggesting that IFN-γ regulates neuronal STAT1-independent pathways to control viral replication.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interferon gama
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Fator de Transcrição STAT1
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Sarampo
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Vírus do Sarampo
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Neurônios
Limite:
Animals
Idioma:
En
Revista:
J Immunol
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos