Wild waterfowl are the reservoirs of avian influenza (AI) viruses and these viruses have the potential to evolve into highly pathogenic avian influenza viruses after transmission to domestic poultry. Various host and viral factors may influence the susceptibility to infection, pathogenicity and transmission of these viruses in wild birds and the main goal of this research is to provide a better understanding of some of these factors. The first objective was to investigate the role of 2,3- and 2,6-linked sialic acid receptors in determining differences in susceptibility to AI viruses in various aquatic and terrestrial wild bird species from different taxa. The results indicate that variations in expression of 2,3- and 2,6-linked sialic acid receptors across taxa do not provide a clear indicator of species-related differences in susceptibility to AI. The second objective was to evaluate the effect of route of inoculation on the infectivity and viral shedding of low pathogenic AI (LPAI) viruses in Mallards. The results of this study showed that Mallards can become infected with LPAI viruses by various routes of inoculation with similar pattern of oropharyngeal and cloacal viral shedding. The third objective was to determine the main sites of LPAI virus replication in Mallards after experimental infection via a natural route of exposure and associate antigen distribution with sialic acid receptor expression. This study revealed that the main sites of LPAI virus replication in Mallards are the enterocytes of the lower intestinal tract and epithelial cells of the bursa of Fabricius, and sialic acid expression in these tissues correlated with viral antigen distribution. The fourth objective was to assess the effect of co-infections with low virulence NDV (loNDV) and LPAI virus on the infectivity and excretion of these viruses in Mallards. Co-infections with these viruses did not affect the ability of Mallards to be infected with either virus and were not detrimental to LPAI virus shedding. Overall, the host and viral factors evaluated in this research were not generally associated with variations in susceptibility of wild birds to AI and did not negatively affect AI virus shedding in Mallards, the natural host of these viruses.