Nonclassical autophagy activation pathways are essential for production of infectious Influenza A virus in vitro.
Tisza A S BellNileena VelappanCheryl D GleasnerGang XieShawn R StarkenburgGeoffrey WaldoShounak BanerjeeSofiya N Micheva-VitevaPublished in: Molecular microbiology (2022)
Autophagy is a critical mechanism deployed by eukaryotic cells in response to stress, including viral infection, to boost the innate antimicrobial responses. However, an increasing number of pathogens hijack the autophagic machinery to facilitate their own replication. Influenza A virus (IAV), responsible for several global pandemics, has an intricate dependence on autophagy for successful replication in mammalian cells. To elucidate key chokepoints in the host stress responses facilitating IAV replication, we constructed a meta-transcriptome of IAV and host gene expression dynamics during early (1-3 hpi), mid (4-6 hpi), and late (8-12 hpi) stages of the viral replication cycle at two multiplicities of infection (MOI): 1 and 5. We supplemented the global transcriptome study with phosphoproteomic analysis of stress-activated protein kinase (SAPK/JNK) signaling in lung carcinoma (predominantly used as an in vitro model of IAV replication) and normal human bronchial epithelial cells. We report significant differences in the activation profiles of autophagy regulating genes upon IAV infection at the two MOI as well as divergent dependence on ULK1 signaling within the normal and cancer cells. Regardless of the cell model, JNK-Thr187 signaling was crucial for the production of infectious viral particles.
Keyphrases
- cell death
- induced apoptosis
- endoplasmic reticulum stress
- signaling pathway
- gene expression
- cell cycle arrest
- single cell
- oxidative stress
- genome wide
- sars cov
- immune response
- rna seq
- endothelial cells
- protein kinase
- dna methylation
- staphylococcus aureus
- stem cells
- mesenchymal stem cells
- cell therapy
- wastewater treatment
- multidrug resistant
- antimicrobial resistance