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

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