Integrative multi-omics analysis in vivo identifies influenza virus host factors
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.
Authors
- Kayla Adkins-Travis (ORCID: https://orcid.org/0000-0002-3410-6597)
- Laura Martin‐Sancho (ORCID: https://orcid.org/0000-0003-1489-2815)
- Judd F. Hultquist (ORCID: https://orcid.org/0000-0001-6424-4280)
- Adolfo Garcı́a-Sastre (ORCID: https://orcid.org/0000-0002-6551-1827)
- Carles Martínez‐Romero (ORCID: https://orcid.org/0000-0001-8888-7715)
- Ethan Stancliffe (ORCID: https://orcid.org/0000-0001-7286-0024)
- Raquel Muñoz-Moreno (ORCID: https://orcid.org/0000-0002-4521-0488)
- Randy A. Albrecht (ORCID: https://orcid.org/0000-0003-4008-503X)
- Jeffrey R. Johnson (ORCID: https://orcid.org/0000-0002-4221-298X)
- Nevan J. Krogan (ORCID: https://orcid.org/0000-0003-4902-337X)
- Gary J. Patti (ORCID: https://orcid.org/0000-0002-3748-6193)
- Manon Eckhardt (ORCID: https://orcid.org/0000-0001-8143-6129)
- Robyn M. Kaake (ORCID: https://orcid.org/0000-0002-8341-3067)
- Lars Pache (ORCID: https://orcid.org/0000-0002-4193-1042)
- Slim Fourati (ORCID: https://orcid.org/0000-0001-6609-7587)
- Rafick‐Pierre Sékaly (ORCID: https://orcid.org/0000-0002-7816-4828)
- Max W. Chang (ORCID: https://orcid.org/0000-0002-4526-489X)
- David A. Stein (ORCID: https://orcid.org/0000-0002-5446-5167)
- Kelsey M. Haas (ORCID: https://orcid.org/0000-0002-1463-6726)
- Christopher Benner (ORCID: https://orcid.org/0000-0002-4618-0719)
- David Jimenez‐Morales (ORCID: https://orcid.org/0000-0003-4356-6461)
- Leah P. Shriver (ORCID: https://orcid.org/0000-0001-5673-0940)
- Yuan Zhou (ORCID: https://orcid.org/0000-0002-1393-5476)
- Erica Stevenson (ORCID: https://orcid.org/0000-0001-7853-1854)
- Celina Cahalane (ORCID: https://orcid.org/0000-0001-6722-6977)
- Sumit K. Chanda (ORCID: https://orcid.org/0000-0001-9399-7927)
- Benjamin J. Polacco (ORCID: https://orcid.org/0000-0003-1570-9234)
- Hong M. Moulton (ORCID: https://orcid.org/0000-0002-8095-1513)
- Danielle L. Swaney (ORCID: https://orcid.org/0000-0001-6119-6084)
- Giorgi Metreveli (ORCID: https://orcid.org/0000-0001-9654-0615)
- Erik Verschueren (ORCID: https://orcid.org/0000-0001-5842-6344)
- Thông Nguyen (ORCID: https://orcid.org/0000-0001-7447-7416)
- Billy W. Newton
- John VonDollen
Institutions
- Scripps Research Institute (US)
- Oregon State University (US)
- Gladstone Institutes (US)
- Emory University (US)
- University of California, San Francisco (US)
- Sanford Burnham Prebys Medical Discovery Institute (US)
- Washington University in St. Louis (US)
- Discovery Institute (US)
- University of California San Diego (US)
- Quantitative BioSciences (US)
- Tisch Hospital (US)
- Oberlin College (US)
- Icahn School of Medicine at Mount Sinai (US)
Publication Details
- Journal
- iScience
- Published
- 2025-09-24
- DOI
- https://doi.org/10.1016/j.isci.2025.113644
- Citations
- 1
- Primary Topic
- Influenza Virus Research Studies
- Type
- article
- Field-Weighted Citation Impact
- 1.35