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

Perot, Brieuc P., Boussier, Jeremy, Yatim, Nader, Rossman, Jeremy S., Ingersoll, Molly, Albert, Matthew (2018) Autophagy diminishes the early interferon- ? response to influenza A virus resulting in differential expression of interferon- stimulated genes. Cell Death & Disease, 9 . Article Number 539. ISSN 2041-4889. (doi:10.1038/s41419-018-0546-5) (KAR id:66887)

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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-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.

Item Type: Article
DOI/Identification number: 10.1038/s41419-018-0546-5
Subjects: Q Science > QR Microbiology > QR180 Immunology
Q Science > QR Microbiology > QR355 Virology
Divisions: Divisions > Division of Natural Sciences > School of Biosciences
Depositing User: Jeremy Rossman
Date Deposited: 02 May 2018 08:54 UTC
Last Modified: 19 Nov 2020 12:39 UTC
Resource URI: https://kar.kent.ac.uk/id/eprint/66887 (The current URI for this page, for reference purposes)
Rossman, Jeremy S.: https://orcid.org/0000-0001-6124-4103
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