Systems Biology Analysis of Mechanism of Host Response to Avian Influenza Virus Infection in Two Genetically Distinct Chicken Inbred Lines

Avian influenza virus (AIV) not only causes significant economic losses in the poultry industry, but also is of major concern to human health. Systems biology analysis is a powerful tool to greatly improve the understanding mechanisms of host response to AIV infection in chickens, by using complex “OMIC” data to expedite breakthroughs in functional genomics/proteomic discovery. Fayoumi and Leghorn inbred chicken lines are, respectively, resistant and susceptible to AIV infection. Chicks were inoculated with 10⁷ EID₅₀ of low pathogenic H5N3 AIV, and lung and tracheae were harvested one and four days post inoculation. RNA-seq and proteomic approaches were integrated to identify genes and signal pathways associated with disease resistance to AIV infection by the dynamic Bayes approach. With AIV infection, Leghorns had greater significantly differentially expressed genes in lung than Fayoumis, while the opposite was observed in tracheae. For proteomic analysis, Leghorns had fewer significantly differentially expressed proteins in lung than Fayoumis. Gene ontology analysis revealed that positive regulation of immune response was down-regulated in Fayoumis, but up-regulated in Leghorns. B and T cell receptor signaling pathways were deactivated in both genetic lines in lungs. In trachea, the T cell receptor signaling pathway was deactivated in both lines and B cell receptor signaling pathway was deactivated in Fayoumi birds and activated in Leghorn birds. Further investigation of the roles of these differentially expressed mRNAs, proteins, and pathways in the regulation of host-AIV interaction can lead in new directions for the development of anti-viral drugs or vaccines in poultry.