Andy
Senior Member (Voting rights)
Highlights
• Integrated multi-omics analysis maps host responses to Influenza infection• Transcriptomic and proteomic data reveal immune and cytoskeletal remodeling
• MidTOD facilitates the integration of metabolomics with other omics datasets
• Mitochondrial enzyme, GATM, identified as a host factor modulating influenza pathogenesis
Summary
Influenza A virus (IAV) infection remodels cellular processes to support viral replication. The modulation of host factors by the virus drives pathogenesis during infection, and these factors may serve as therapeutic targets. Here, we infect mice with two IAV strains, H1N1 and H5N1, and analyze lung tissue with multi-omics. Using network propagation analysis, we identify twenty-four distinct host modules altered by infection, encompassing 2920 genes/proteins. Independently, we develop a computational pipeline, MidTOD, which integrates metabolomic data with other OMICs data-types, linking metabolites to gene/protein alterations. Combining datasets from both approaches reveals alterations in mitochondrial and peroxisomal metabolism in IAV-infected cells and identifies arginine:glycine amidinotransferase (GATM) as a host dependency factor in both human cells and mice. Knockdown of this enzyme reduces IAV-mediated pathology and host inflammatory responses after infection. Collectively, this work provides an integrated systems-level view of host changes during infection and identifies an abundance of IAV-host factors.Open access