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Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

American Society for MicrobiologyJournal of Virology

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Macaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections

  1. Joseph N. Brown1,
  2. Robert E. Palermo2,3,
  3. Carole R. Baskin2,3,,
  4. Marina Gritsenko1,
  5. Patrick J. Sabourin4,
  6. James P. Long4,
  7. Carol L. Sabourin4,
  8. Helle Bielefeldt-Ohmann5,§,
  9. Adolfo García-Sastre6,7,8,
  10. Randy Albrecht6,8,
  11. Terrence M. Tumpey9,
  12. Jon M. Jacobs1,
  13. Richard D. Smith1 and
  14. Michael G. Katze2,3,*
  1. 1Biological Sciences Division and Environmental Molecular Sciences Laboratory, Pacific Northwest National Laboratories, Richland, Washington 99352
  2. 2Department of Microbiology
  3. 3Washington National Primate Research Center, University of Washington, Seattle, Washington 98195
  4. 4Battelle Biomedical Research Center, West Jefferson, Ohio 43201
  5. 5Department of Microbiology, Immunology and Pathology, Colorado State University, Fort Collins, Colorado 80523
  6. 6Departments of Microbiology
  7. 7Medicine, Division of Infectious Diseases
  8. 8Emerging Pathogens Institute, Mount Sinai School of Medicine, New York, New York 10029
  9. 9Influenza Division, Centers for Disease Control and Prevention, Atlanta, Georgia 30333


The host proteome response and molecular mechanisms that drive disease in vivo during infection by a human isolate of the highly pathogenic avian influenza virus (HPAI) and 1918 pandemic influenza virus remain poorly understood. This study presents a comprehensive characterization of the proteome response in cynomolgus macaque (Macaca fascicularis) lung tissue over 7 days of infection with HPAI (the most virulent), a reassortant virus containing 1918 hemagglutinin and neuraminidase surface proteins (intermediate virulence), or a human seasonal strain (least virulent). A high-sensitivity two-dimensional liquid chromatography-tandem mass spectroscopy strategy and functional network analysis were implemented to gain insight into response pathways activated in macaques during influenza virus infection. A macaque protein database was assembled and used in the identification of 35,239 unique peptide sequences corresponding to approximately 4,259 proteins. Quantitative analysis identified an increase in expression of 400 proteins during viral infection. The abundance levels of a subset of these 400 proteins produced strong correlations with disease progression observed in the macaques, distinguishing a “core” response to viral infection from a “high” response specific to severe disease. Proteome expression profiles revealed distinct temporal response kinetics between viral strains, with HPAI inducing the most rapid response. While proteins involved in the immune response, metabolism, and transport were increased rapidly in the lung by HPAI, the other viruses produced a delayed response, characterized by an increase in proteins involved in oxidative phosphorylation, RNA processing, and translation. Proteomic results were integrated with previous genomic and pathological analysis to characterize the dynamic nature of the influenza virus infection process.


    • Received 26 May 2010.
    • Accepted 3 September 2010.
  • *Corresponding author. Mailing address: Department of Microbiology, Washington National Primate Research Center, Box 358070, Seattle, WA 98195. Phone: (206) 732-6135. Fax: (206) 732-6056. E-mail: honey{at}
  • ‡ Present address: Science Foundation Arizona, 400 East Van Buren Street, Phoenix, AZ 85004.

  • § Present address: University of Queensland, St. Lucia, Queensland 4072, Australia.

  • ▿ Published ahead of print on 15 September 2010.

  • † Supplemental material for this article may be found at [].

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  1. Accepted manuscript posted online 15 September 2010, doi: 10.1128/JVI.01129-10 J. Virol. November 2010 vol. 84 no. 22 12058-12068
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