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Abstract
Influenza A (IAV) virus remains a major pathogen of humans and animals. H9N2 viruses are low pathogenic avian influenza viruses and are currently the most widespread influenza virus in land-based poultry. In recent years, H9 viruses have begun to acquire molecular characteristics that make them more human like as well as contribute to the evolution of influenza viruses by donating genes to emerging IAVs. In the first part of this thesis, we characterized the effects of ferret adapted molecular changes on the replication and transmission of reassortant viruses in natural hosts of influenza. We found that molecular changes associated with mammalian transmission in ferrets are viable in pigs and are not detrimental in quails. We further identified a role for the internal gene constellation for reassortant virus replication in different species.The entry of influenza virus is initiated by the HA (Hemagglutinin) binding to sialic acid (SA) cellular receptor via its receptor-binding site (RBS). In general, avian influenza viruses bind 2,3SA while human viruses prefer 2,6SA in concert with the abundance of these SAs in these hosts. Changes in the HA can alter SA preference and modulate host range of influenza viruses. In the final part of this thesis, we focused on determining the plasticity of amino acid at position 226, a position associated with a shift in receptor recognition. We identified a diverse set of amino acids that were tolerated at this position, some of which have yet to be found in natural isolates and determined by in-vitro studies the fitness and receptor specificity of these alternative variants. Taken together this body of work expands our understanding of the effects of molecular changes on the surface proteins of influenza viruses and broadens existing knowledge on the effects of single amino acid changes in the HA.