Open AccessMacaque Proteome Response to Highly Pathogenic Avian Influenza and 1918 Reassortant Influenza Virus Infections
Author(s) -
Joseph N. Brown,
Robert E. Palermo,
Carole R. Baskin,
Marina Gritsenko,
Patrick J. Sabourin,
James P. Long,
Carol L. Sabourin,
Helle BielefeldtOhmann,
Adolfo Garcı́a-Sastre,
Randy A. Albrecht,
Terrence M. Tumpey,
Jon Jacobs,
Richard Smith,
Michael G. Katze
Publication year - 2010
Publication title -
journal of virology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.617
H-Index - 292
eISSN - 1070-6321
pISSN - 0022-538X
DOI - 10.1128/jvi.01129-10
Subject(s) - biology , virology , influenza a virus subtype h5n1 , macaque , h5n1 genetic structure , influenza a virus , highly pathogenic , virus , proteome , orthomyxoviridae , microbiology and biotechnology , genetics , infectious disease (medical specialty) , covid-19 , disease , paleontology , medicine , pathology
The host proteome response and molecular mechanisms that drive diseasein 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.