tetano
Editor, Senior Moderator
iScience
. 2025 Sep 24;28(11):113644.
doi: 10.1016/j.isci.2025.113644. eCollection 2025 Nov 21. Integrative multi-omics analysis in vivo identifies influenza virus host factors
Leah P Shriver[SUP] 1 2 3 [/SUP], Benjamin J Polacco[SUP] 4 5 6 [/SUP], Manon Eckhardt[SUP] 4 5 6 [/SUP], Max W Chang[SUP] 7 [/SUP], Carles Martínez-Romero[SUP] 8 9 [/SUP], Kayla Adkins-Travis[SUP] 1 2 3 [/SUP], Celina Cahalane[SUP] 10 [/SUP], Kelsey Haas[SUP] 4 5 6 [/SUP], David A Stein[SUP] 11 [/SUP], Slim Fourati[SUP] 12 [/SUP], Laura Martin-Sancho[SUP] 13 [/SUP], Giorgi Metreveli[SUP] 8 9 [/SUP], Jeffrey R Johnson[SUP] 4 5 6 8 [/SUP], Raquel Muñoz-Moreno[SUP] 8 9 [/SUP], Billy W Newton[SUP] 5 6 [/SUP], Robyn M Kaake[SUP] 4 5 6 [/SUP], Yuan Zhou[SUP] 4 5 6 [/SUP], David Jimenez-Morales[SUP] 4 5 6 [/SUP], John VonDollen[SUP] 4 5 6 [/SUP], Erik Verschueren[SUP] 5 6 [/SUP], Danielle L Swaney[SUP] 4 5 6 14 [/SUP], Thong T Nguyen[SUP] 4 5 6 [/SUP], Erica J Stevenson[SUP] 4 5 6 [/SUP], Ethan Stancliffe[SUP] 1 2 3 [/SUP], Gary J Patti[SUP] 1 2 3 [/SUP], Randy Albrecht[SUP] 8 9 [/SUP], Hong M Moulton[SUP] 11 [/SUP], Lars Pache[SUP] 15 [/SUP], Rafick P Sekaly[SUP] 12 [/SUP], Christopher Benner[SUP] 7 [/SUP], Judd F Hultquist[SUP] 4 5 6 [/SUP], Sumit K Chanda[SUP] 15 13 [/SUP], Adolfo Garcia-Sastre[SUP] 8 9 16 17 18 [/SUP], Nevan J Krogan[SUP] 4 5 6 14 [/SUP]
Affiliations
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.
Keywords: Biocomputational method; Metabolomics; Model organism; Proteomics; Transcriptomics; Virology.
. 2025 Sep 24;28(11):113644.
doi: 10.1016/j.isci.2025.113644. eCollection 2025 Nov 21. Integrative multi-omics analysis in vivo identifies influenza virus host factors
Leah P Shriver[SUP] 1 2 3 [/SUP], Benjamin J Polacco[SUP] 4 5 6 [/SUP], Manon Eckhardt[SUP] 4 5 6 [/SUP], Max W Chang[SUP] 7 [/SUP], Carles Martínez-Romero[SUP] 8 9 [/SUP], Kayla Adkins-Travis[SUP] 1 2 3 [/SUP], Celina Cahalane[SUP] 10 [/SUP], Kelsey Haas[SUP] 4 5 6 [/SUP], David A Stein[SUP] 11 [/SUP], Slim Fourati[SUP] 12 [/SUP], Laura Martin-Sancho[SUP] 13 [/SUP], Giorgi Metreveli[SUP] 8 9 [/SUP], Jeffrey R Johnson[SUP] 4 5 6 8 [/SUP], Raquel Muñoz-Moreno[SUP] 8 9 [/SUP], Billy W Newton[SUP] 5 6 [/SUP], Robyn M Kaake[SUP] 4 5 6 [/SUP], Yuan Zhou[SUP] 4 5 6 [/SUP], David Jimenez-Morales[SUP] 4 5 6 [/SUP], John VonDollen[SUP] 4 5 6 [/SUP], Erik Verschueren[SUP] 5 6 [/SUP], Danielle L Swaney[SUP] 4 5 6 14 [/SUP], Thong T Nguyen[SUP] 4 5 6 [/SUP], Erica J Stevenson[SUP] 4 5 6 [/SUP], Ethan Stancliffe[SUP] 1 2 3 [/SUP], Gary J Patti[SUP] 1 2 3 [/SUP], Randy Albrecht[SUP] 8 9 [/SUP], Hong M Moulton[SUP] 11 [/SUP], Lars Pache[SUP] 15 [/SUP], Rafick P Sekaly[SUP] 12 [/SUP], Christopher Benner[SUP] 7 [/SUP], Judd F Hultquist[SUP] 4 5 6 [/SUP], Sumit K Chanda[SUP] 15 13 [/SUP], Adolfo Garcia-Sastre[SUP] 8 9 16 17 18 [/SUP], Nevan J Krogan[SUP] 4 5 6 14 [/SUP]
Affiliations
- PMID: 41142120
- PMCID: PMC12552919
- DOI: 10.1016/j.isci.2025.113644
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.
Keywords: Biocomputational method; Metabolomics; Model organism; Proteomics; Transcriptomics; Virology.