Format

Send to

Choose Destination
Cell Host Microbe. 2016 Feb 10;19(2):254-66. doi: 10.1016/j.chom.2016.01.002.

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

Author information

1
Department of Microbiology, University of Washington, Seattle, WA 98195, USA.
2
Department of Pathobiological Sciences, School of Veterinary Medicine, University of Wisconsin, Madison, WI 53706, USA.
3
Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
4
Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
5
Computational and Statistical Analytics Division, Pacific Northwest National Laboratory, Richland, WA 99354, USA.
6
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.
7
Laboratoire de Virologie, Centre de Biologie Est des Hospices Civils de Lyon, Université Claude Bernard Lyon 1, 69495 Lyon, France.
8
Department of Microbiology, University of Washington, Seattle, WA 98195, USA; Washington National Primate Research Center, Seattle, WA 98195, USA. Electronic address: honey@uw.edu.

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.

PMID:
26867183
PMCID:
PMC5271177
DOI:
10.1016/j.chom.2016.01.002
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Elsevier Science Icon for PubMed Central
Loading ...
Support Center