Receptor binding specificities of influenza A viruses beyond the sialic acid linkage

Influenza A viruses are responsible for millions of deaths and cases of severe illness annually in humans and animals. New virus particles are produced inside cells and therefore the first step in the infection cycle involves influenza A virus particles binding to the cell surface. On the cell surface, the viruses bind to chains of sugar molecules (glycans). Glycans can vary a lot in, for example, the length, composition of sugar molecules in the chain, and connections between the sugar molecules. The spread of influenza A viruses from birds, a species in which a lot of these viruses occur, to humans poses a big risk. Therefore, traditionally, a lot of studies have been performed on the transmission of these viruses from birds to humans. Influenza A viruses bind to sialic acids, a specific type of sugar molecule that is present on the end of glycan chains. The glycans in birds and humans are different because the sialic acids are linked differently to the rest of the glycan. In birds, the sialic acids are mostly α2,3-linked, while in humans the α2,6-linkage is most common, which poses a species barrier that may prevent virus transmission between species. In this dissertation, we aimed to investigate the fine receptor specificities of IAVs and the molecular determinants responsible for this binding, looking beyond the classically considered α2,3-linked and α2,6-linked Neu5Ac. We aimed to investigate biologically relevant N-glycan cores presenting a diverse repertoire of epitopes, such as elongated branches, multiple branches, Neu5Ac, Neu5Gc, and sLeX epitopes.