title: Integrated Omics Analysis of Pathogenic Host Responses during Pandemic H1N1 Influenza Virus Infection: The Crucial Role of Lipid Metabolism.
abstract: 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.
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Jennifer
authors: J
authors: Tisoncik-Go
authors: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors: David J
authors: DJ
authors: Gasper
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Jennifer E
authors: JE
authors: Kyle
authors: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors: Amie J
authors: AJ
authors: Eisfeld
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Christian
authors: C
authors: Selinger
authors: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors: Masato
authors: M
authors: Hatta
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Juliet
authors: J
authors: Morrison
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Marcus J
authors: MJ
authors: Korth
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Erika M
authors: EM
authors: Zink
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Young-Mo
authors: YM
authors: Kim
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Athena A
authors: AA
authors: Schepmoes
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Carrie D
authors: CD
authors: Nicora
authors: Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Samuel O
authors: SO
authors: Purvine
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Karl K
authors: KK
authors: Weitz
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Xinxia
authors: X
authors: Peng
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
authors: Richard R
authors: RR
authors: Green
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Susan C
authors: SC
authors: Tilton
authors: Computational and Statistical Analytics Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Bobbie-Jo
authors: BJ
authors: Webb-Robertson
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Katrina M
authors: KM
authors: Waters
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Thomas O
authors: TO
authors: Metz
authors: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
authors: Richard D
authors: RD
authors: Smith
authors: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA; Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Japan Department of Special Pathogens, International Research Center for Infectious Diseases, Institute of Medical Science, University of Tokyo, Minato-ku, Tokyo 108-8639, Japan; Laboratory of Bioresponses Regulation, Department of Biological Responses, Institute for Virus Research, Kyoto University, Kyoto 606-8507, Japan.
authors: Yoshihiro
authors: Y
authors: Kawaoka
authors: Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
authors: M
authors: M
authors: Suresh
authors: Laboratoire de Virologie, Centre de Biologie Est des Hospices Civils de Lyon, Université Claude Bernard Lyon 1, 69495 Lyon, France.
authors: Laurence
authors: L
authors: Josset
authors: Department of Microbiology, University of Washington, Seattle, WA 98195, USA; Washington National Primate Research Center, Seattle, WA 98195, USA. Electronic address: honey@uw.edu.
authors: Michael G
authors: MG
authors: Katze
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005289:Ferrets; D015870:Gene Expression; D054884:Host-Pathogen Interactions; D006801:Humans; D053118:Influenza A Virus, H1N1 Subtype / Q000502:physiology*; D007251:Influenza, Human / Q000453:epidemiology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry; D008168:Lung / Q000378:metabolism / Q000473:pathology / Q000821:virology; D055432:Metabolomics
chemical_list: D008055:Lipids