Specific mutations in H5N1 mainly impact the magnitude and velocity of the host response in mice Public Deposited

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Creator
  • Metz, Thomas O
    • Other Affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
  • Eisfeld, Amie J
    • Other Affiliation: School of Veterinary Medicine, Department of Pathobiological Sciences, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, USA
  • Ferris, Martin T
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Tilton, Susan C
    • Other Affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
  • Baric, Ralph S.
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Kawaoka, Yoshihiro
    • Other Affiliation: School of Veterinary Medicine, Department of Pathobiological Sciences, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, USA
  • Josset, Laurence
    • Other Affiliation: Department of Microbiology, University of Washington, Seattle, WA 98195 USA
  • Katze, Michael G
    • Other Affiliation: Department of Microbiology; Washington National Primate Research Center, University of Washington, Seattle, WA, USA
  • Tisoncik-Go, Jennifer
    • Other Affiliation: Department of Microbiology, University of Washington, Seattle, WA 98195 USA
  • Gralinski, Lisa E
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Bécavin, Christophe
    • Other Affiliation: Unité des Interactions Bactéries-Cellules, Institut Pasteur, 75015 Paris, France
  • Neumann, Gabriele
    • Other Affiliation: School of Veterinary Medicine, Department of Pathobiological Sciences, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, USA
  • Waters, Katrina M
    • Other Affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
  • Totura, Allison L
    • Affiliation: School of Medicine, Department of Microbiology and Immunology
  • Li, Chengjun
    • Other Affiliation: School of Veterinary Medicine, Department of Pathobiological Sciences, Influenza Research Institute, University of Wisconsin-Madison, Madison, WI, USA
  • Tchitchek, Nicolas
    • Other Affiliation: Department of Microbiology, University of Washington, Seattle, WA 98195 USA
  • Smith, Richard D
    • Other Affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
  • Webb-Robertson, Bobbie-Jo
    • Other Affiliation: Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, USA
Abstract
  • Background: Influenza infection causes respiratory disease that can lead to death. The complex interplay between virus-encoded and host-specific pathogenicity regulators – and the relative contributions of each toward viral pathogenicity – is not well-understood. Results: By analyzing a collection of lung samples from mice infected by A/Vietnam/1203/2004 (H5N1; VN1203), we characterized a signature of transcripts and proteins associated with the kinetics of the host response. Using a new geometrical representation method and two criteria, we show that inoculation concentrations and four specific mutations in VN1203 mainly impact the magnitude and velocity of the host response kinetics, rather than specific sets of up- and down- regulated genes. We observed analogous kinetic effects using lung samples from mice infected with A/California/04/2009 (H1N1), and we show that these effects correlate with morbidity and viral titer. Conclusions: We have demonstrated the importance of the kinetics of the host response to H5N1 pathogenesis and its relationship with clinical disease severity and virus replication. These kinetic properties imply that time-matched comparisons of ‘omics profiles to viral infections give limited views to differentiate host-responses. Moreover, these results demonstrate that a fast activation of the host-response at the earliest time points post-infection is critical for protective mechanisms against fast replicating viruses.
Date of publication
Identifier
  • 23895213
  • doi:10.1186/1752-0509-7-69
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Nicolas Tchitchek et al.; licensee BioMed Central Ltd.
License
Journal title
  • BMC Systems Biology
Journal volume
  • 7
Journal issue
  • 1
Page start
  • 69
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1752-0509
Bibliographic citation
  • BMC Systems Biology. 2013 Jul 29;7(1):69
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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