Proteomic analyses of seasonal human respiratory viruses unravel changes related to antiviral, inflammatory, and cell death pathways.

Newly emerging and re-emerging viruses are of significant global concern. Several viruses cause significant respiratory distress, including human coronaviruses (hCoVs), influenza A viruses (IAVs), and respiratory syncytial virus (RSV). Viruses usurp and modify host cellular processes to successfully replicate. We used quantitative label-free mass spectrometry-based proteomic analyses of transformed human lung A549 cells infected with representative seasonal hCoV, IAV, and RSV at 24 h post-infection to delineate comparative virus-induced host cell alterations. Numerous proteins involved in lipid metabolism, molecular transport, cell death and survival, and inflammatory responses were dysregulated. RSV induced a more profound response in cellular protein quantities than either CoV or IAV. The most significantly affected proteins were enzymes, ion channels, kinases, transcription regulators, and transmembrane receptors. Many canonical pathways also were differentially affected by each virus. The altered expression of proteins and pathways may provide insights into future therapeutic interventions for these viral infections.