Molecular Characterization Of The Hemagglutinin Receptor-binding Specificity Of Avian Influenza Viruses: Predicting The Jump Across The Species Barrier | 35398
Journal of Infectious Diseases & Therapy
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Influenza is a constant global burden to human health. Seasonal influenza results in significant infections and death, cycling
through both hemispheres. On occasion, a novel avian influenza virus crosses the species barrier from birds to humans
resulting in an influenza pandemic. The threat of pandemic avian influenza continues with H5N1 and H7N9 consistently
infecting humans. In order to evolve from its avian form and gain the pandemic potential for increased transmissibility
between humans, the Hem-Agglutinin (HA) of avian influenza viruses will need to undergo mutations in its Receptor Binding
Site (RBS) that bring about an avian to human receptor preference switch. In order to understand the major determinants of
virus transmissibility and the pandemic potential of the novel avian influenza viruses, we have determined the crystallographic
structure of the novel avian influenza H10N7 A/Turkey/MN/3/79 to 1.96Å and mapped the RBS. The amino acid residues
responsible for conferring receptor selectivity were identified by site-direct mutagenesis of recombinant H10 HA proteins. The
receptor-binding selectivity of the HAs was determined using sialyl glycan binding assays. Docking models were constructed
of the H10 HA in complex with α2, 6-sialic acid (human) and α2, 3-sialic acid (avian) penta-saccharide receptor analogs to
ascertain the correlation between the binding assay data and the interactions within the receptor binding pocket. The present
findings provided a structure-recognition perspective for the receptor binding properties of the novel avian H10 influenza HA.
Tony Velkov completed PhD from Monash University in the year 2000. His anti-infective discovery research is at the leading edge globally. He was awarded an NHMRC Research Fellowships. The quality and impact of his independent research was recognized by the NHMRC with an Excellence Award. He has published over 50 papers in high caliber journals, 3 book chapters and 15 conference presentations. The dynamic team he leads consists of 3 Post-docs, 3 RAs and 9 PhD students. Over the last 6 years, he has obtained >$9M funding from the NIH, NHMRC and foundations.