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

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

The impact of macroautophagy on CD8 + T-cell-mediated antiviral immunity

International audienceMacroautophagy is a catabolic recycling pathway, which can be induced by various stress stimuli. Viruses are able to manipulate autophagy in the cells that they infect. The impact of autophagy on the innate immune response to viruses and its stimulatory role in antigen presentation to CD4(+) T cells are well documented. Herein, we present the impact of autophagy on the activation of cytotoxic T lymphocyte (CTL)-mediated antiviral immune responses, which are required for the eradication or control of multiple viruses. We first discuss the general mechanisms by which viruses can either induce or block autophagy in cells. We then explore the cross-talk between autophagy and innate immune processes, which are both first line defenses against viruses; and constitute crucial steps for the initiation of potent adaptive immune responses. We describe the impact of autophagy on the presentation of viral peptide antigens on class I major histocompatibility complex (MHC I), a prerequisite for the priming of CTL responses. In sum, our review highlights the interplay between viruses and three integrated host response pathways - autophagy, innate and adaptive immunity - providing a framework for future mechanistic and pathogenesis-based research