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Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism Public Deposited

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  • Pandemic influenza viruses modulate proinflammatory responses that can lead to immunopathogenesis. We present an extensive and systematic profiling of lipids, metabolites, and proteins in respiratory compartments of ferrets infected with either 1918 or 2009 human pandemic H1N1 influenza viruses. Integrative analysis of high-throughput omics data with virologic and histopathologic data uncovered relationships between host responses and phenotypic outcomes of viral infection. Proinflammatory lipid precursors in the trachea following 1918 infection correlated with severe tracheal lesions. Using an algorithm to infer cell quantity changes from gene expression data, we found enrichment of distinct T cell subpopulations in the trachea. There was also a predicted increase in inflammatory monocytes in the lung of 1918 virus-infected animals that was sustained throughout infection. This study presents a unique resource to the influenza research community and demonstrates the utility of an integrative systems approach for characterization of lipid metabolism alterations underlying respiratory responses to viruses.
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  • Tisoncik-Go, J., Gasper, D. J., Kyle, J. E., Eisfeld, A. J., Selinger, C., Hatta, M., ... & Katze, Michael G. (2016). Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism. Cell Host & Microbe, 19(2), 254-266. doi:10.1016/j.chom.2016.01.002
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  • 19
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  • 2
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  • This project has been funded in whole or in part with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under CEIRS contract number HHSN272201400006C and contract number HHSN272201400005C. Additional support was provided by Public Health Service grants P51OD010425 and U19AI109761 from the National Institutes of Health. D.J.G. was supported by NIH training grant 5T32OD010423-07 and through The American Association of Immunologists Careers in Immunology Fellowship Program. The proteomics, metabolomics, and lipidomics measurements were conducted using capabilities developed under NIGMS Grant P41 GM103493 and the U.S. Department of Energy (DOE)-supported Pan-omics Program, and were performed in the Environmental Molecular Science Laboratory, a DOE national scientific user facility at Pacific Northwest National Laboratory (PNNL) in Richland, WA. PNNL is a multiprogram national laboratory operated by Battelle for the DOE under contract DE-AC05-76RLO 1830.
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