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

Area of Science:

• Virology and Host-Pathogen Interactions
• Proteomics and Systems Biology
• Infectious Disease Pathogenesis

Background:

• Understanding host responses to influenza viruses, particularly highly pathogenic avian influenza (HPAI) and the 1918 pandemic strain, is crucial for disease control.
• In vivo molecular mechanisms driving pathogenesis during infection with these virulent influenza strains remain incompletely understood.
• Cynomolgus macaques serve as a relevant model for studying human influenza infections.

Purpose of the Study:

• To comprehensively characterize the host proteome response in macaque lung tissue following infection with HPAI, a 1918 reassortant, and a seasonal influenza strain.
• To identify molecular pathways and protein expression changes associated with varying virulence levels and disease progression.
• To elucidate the temporal dynamics of the host proteome response to different influenza virus strains.

Main Methods:

• High-sensitivity two-dimensional liquid chromatography-tandem mass spectrometry (2D-LC-MS/MS) was employed for proteomic analysis.
• A custom macaque protein database was developed for accurate protein identification and quantification.
• Functional network analysis and correlation with disease progression were used to interpret proteomic data.

Main Results:

• Over 4,259 proteins were identified, with 400 showing increased expression during viral infection.
• A subset of these proteins correlated with disease severity, distinguishing a core viral response from a severe disease response.
• Distinct temporal proteome kinetics were observed: HPAI induced a rapid immune, metabolic, and transport protein response, while other strains elicited a delayed response involving oxidative phosphorylation, RNA processing, and translation.

Conclusions:

• Proteomic profiling reveals distinct host responses to influenza virus strains of differing virulence in macaques.
• HPAI elicits a rapid, distinct proteome signature compared to less virulent strains, highlighting strain-specific pathogenic mechanisms.
• Integration of proteomic data with genomic and pathological findings provides a dynamic view of influenza virus infection progression.