Autophagy diminishes the early interferon-ß response to influenza A virus resulting in differential expression of interferon-stimulated genes.
Cell Death Dis
; 9(5): 539, 2018 05 01.
Article
en En
| MEDLINE
| ID: mdl-29748576
ABSTRACT
Influenza A virus (IAV) infection perturbs metabolic pathways such as autophagy, a stress-induced catabolic pathway that crosstalks with cellular inflammatory responses. However, the impact of autophagy perturbation on IAV gene expression or host cell responses remains disputed. Discrepant results may be a reflection of in vivo studies using cell-specific autophagy-related (Atg) gene-deficient mouse strains, which do not delineate modification of developmental programmes from more proximal effects on inflammatory response. In vitro experiments can be confounded by gene expression divergence in wild-type cultivated cell lines, as compared to those experiencing long-term absence of autophagy. With the goal to investigate cellular processes within cells that are competent or incompetent for autophagy, we generated a novel experimental cell line in which autophagy can be restored by ATG5 protein stabilization in an otherwise Atg5-deficient background. We confirmed that IAV induced autophagosome formation and p62 accumulation in infected cells and demonstrated that perturbation of autophagy did not impact viral infection or replication in ATG5-stablized cells. Notably, the induction of interferon-stimulated genes (ISGs) by IAV was diminished when cells were autophagy competent. We further demonstrated that, in the absence of ATG5, IAV-induced interferon-ß (IFN-ß) expression was increased as compared to levels in autophagy-competent lines, a mechanism that was independent of IAV non-structural protein 1. In sum, we report that induction of autophagy by IAV infection reduces ISG expression in infected cells by limiting IFN-ß expression, which may benefit viral replication and spread.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Virus de la Influenza A
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Regulación de la Expresión Génica
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Interferón beta
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Infecciones por Orthomyxoviridae
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Autofagosomas
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Proteína 5 Relacionada con la Autofagia
Límite:
Animals
Idioma:
En
Revista:
Cell Death Dis
Año:
2018
Tipo del documento:
Article
País de afiliación:
Francia