WP4 - Receptor specificity and innate immunity

Partners involved:
N° 4, Dr. Mikhail Matrosovich (WP Leader)
N° 2, Dr. Stefania Crotta
N° 3, Prof. Kristien Van Reeth

Limited available data suggest that receptor specificity and sialidase activity of influenza viruses can affect innate immune responses to the virus and thus determine its pathogenicity. The goal of WP4 is to test this hypothesis in airway epithelial cells and in immuno-competent cells. To address these questions, we will use natural and recombinant influenza viruses with distinct receptor specificities. H5N1 viruses and 1918 viruses will be included in the study to test whether distinctive receptor specificities of these viruses contribute to their high pathogenicity. We will test how infection with live viruses (as well as binding to cells of killed viruses) affects expression of genes and cellular responses in differentiated cultures of human airway epithelium and in isolated human immuno-competent cells (macrophages, dendritic cells, T- and B-lymphocytes, neutrophils, NK-cells). Based on these data and using the same virus panels, we will test whether viral receptor specificity affects innate responses in several animal models (mice, pigs, and ferrets). New information on the role of HA and NA in pathogenicity of influenza viruses will improve surveillance for emerging influenza viruses and will provide the rationale for new approaches to influenza prophylaxis and treatment. Furthermore, this work may result in establishing a new standard, namely receptor specificity, for the characterisation of influenza virus strains and vaccines.