Determination of the glycointeractome of influenza A virus

Glycans with a terminal sialic acid residue have long been considered to be the sole receptor for the two major surface glycoproteins haemagglutinin (HA) and neuraminidase (NA) of influenza A virus. It has been suggested that also the inner parts of the glycans and asialo-glycans are involved in the interactions of the virus with the host cell. In this study I aim to analyse systematically the binding epitopes of cellular carbohydrates, which are in direct contact with the HA and NA proteins of (i) seasonal human and pandemic swine H1N1, (ii) animal-to-human- transmissible H5N1, H7N7, H9N2 and H7N3, (iii) human-adapted H2N2 and H3N2 and (iv) the Tamiflu-resistant N1-H274Y mutant by glycan array, saturation transfer difference (STD) NMR spectroscopy and surface plasmon resonance (SPR) techniques. On the basis of the obtained data I will establish a glycan interaction map (glycointeractome) of influenza A virus to determine key glycans, which are the main cell surface receptors. This glycointeractome will not only advance our knowledge of the crucial relation between receptor specificity and host cell tropism but it will also provide structural basis for the design and development of the next generation of anti- influenza drugs and vaccines.