Abstract

Elucidation of molecular pathogenesis underlying virus-host interaction is important for the development of new diagnostic and therapeutic strategies against highly pathogenic avian influenza (HPAI) infection in chicken. However, chicken HPAI viral pathogenesis is not completely understood. To elucidate the intracellular signaling pathways and critical host proteins associated with influenza pathogenesis, we characterized the lung proteome of chicken infected with HPAI H5N1 virus (A/duck/India/02CA10/2011/Agartala). The chicken mass spectra data sets comprised1, 47, 451 MS scans and 19, 917 MS/MS scans. At local FDR 5% level, we identified total 3313 chicken proteins with presence of at least one unique peptide. At 12 hrs, 247 proteins are downregulated while 1754 proteins are downregulated at 48 hrs indicating that the host has succumbed to infection. There is expression of proteins of the predominant signaling pathways, such as TLR, RLR, NLR and JAK-STAT signaling. Activation of these pathways is associated with cytokine storm effect and thus may be the cause of severity of HPAI H5N1 infection in chicken. Further we identified proteins like MyD88, IKBKB, IRAK4, RELA, and MAVS involved in the critical signaling pathways and some other novel proteins(HNF4A, ELAVL1, FN1, COPS5, CUL1, BRCA1 and FYN) as main hub proteins that might play important roles in influenza pathogenesis in chicken. Taken together, we characterized the signaling pathways and the proteomic determinants responsible for disease pathogenesis in chicken infected with HPAI H5N1 virus.