Autophagy diminishes the early interferon-β response to influenza A virus resulting in differential expression of interferon-stimulated genes - Université Denis Diderot - Paris VII Accéder directement au contenu
Article Dans Une Revue Cell Death and Disease Année : 2018

Autophagy diminishes the early interferon-β response to influenza A virus resulting in differential expression of interferon-stimulated genes

Résumé

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-β (IFN-β) 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-β expression, which may benefit viral replication and spread.

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Immunologie
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Dates et versions

hal-01798006 , version 1 (23-05-2018)

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Brieuc P. Perot, Jeremy Boussier, Nader Yatim, Jeremy S Rossman, Molly A Ingersoll, et al.. Autophagy diminishes the early interferon-β response to influenza A virus resulting in differential expression of interferon-stimulated genes. Cell Death and Disease, 2018, 9, pp.539. ⟨10.1038/s41419-018-0546-5⟩. ⟨hal-01798006⟩
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