U.S. Department of Energy

Pacific Northwest National Laboratory

Macaque proteome response to highly pathogenic avian influenza and 1918 reassortant influenza virus infections.

TitleMacaque proteome response to highly pathogenic avian influenza and 1918 reassortant influenza virus infections.
Publication TypeJournal Article
Year of Publication2010
AuthorsBrown JN, Palermo RE, Baskin CR, Gritsenko M, Sabourin PJ, Long JP, Sabourin CL, Bielefeldt-Ohmann H, García-Sastre A, Albrecht R, Tumpey TM, Jacobs JM, Smith RD, Katze MG
JournalJ Virol
KeywordsAnimals, Disease Models, Animal, Female, Humans, Influenza A virus, Influenza, Human, Lung, Macaca fascicularis, Male, Proteins, Proteome, Reassortant Viruses, Virulence
Abstract

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.

DOI10.1128/JVI.01129-10
Alternate JournalJ. Virol.
PubMed ID20844032
PubMed Central IDPMC2977874
Grant ListK08 AI059106-02 / AI / NIAID NIH HHS / United States
P01AI58113 / AI / NIAID NIH HHS / United States
P51 RR00166-45 / RR / NCRR NIH HHS / United States
R01 AI022646-20A1 / AI / NIAID NIH HHS / United States
R01AI46954 / AI / NIAID NIH HHS / United States
R03 AI075019-01 / AI / NIAID NIH HHS / United States
R24 OD011157 / OD / NIH HHS / United States
R24 RR016354-09 / RR / NCRR NIH HHS / United States
R24 RR16354-04 / RR / NCRR NIH HHS / United States
RR018522 / RR / NCRR NIH HHS / United States
U19AI083025 / AI / NIAID NIH HHS / United States
U54AI057158 / AI / NIAID NIH HHS / United States
Supplemental Materials: 
| Pacific Northwest National Laboratory