Perot BP, Boussier J, Yatim N. Autophagy diminishes the early interferon-β response to influenza A virus resulting in differential expression of interferon-stimulated genes. Cell Death Dis. 2018 May 10;9(5):539.
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.
See Also:
Latest articles in those days:
- Host restriction factor SAMHD1 does not restrict seasonal influenza virus replication in human epithelial or macrophage-like cells 5 hours ago
- Enhancing the stability of Influenza A reporter viruses by recoding the gfp gene 5 hours ago
- T cell help is a limiting factor for rare anti-influenza memory B cells to reenter germinal centers and generate potent broadly neutralizing antibodies 2 days ago
- Wild birds drive the introduction, maintenance, and spread of H5N1 clade 2.3.4.4b high pathogenicity avian influenza viruses in Spain, 2021-2022 2 days ago
- [preprint]FluNexus: a versatile web platform for antigenic prediction and visualization of influenza A viruses 2 days ago
[Go Top] [Close Window]


