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Monitoring influenza virus receptor binding changes by biophysical and structural analyses Alex Xiaoli Xiong Abstract Influenza viruses currently established in the population are believed to originate from zoonotic influenza viruses through human adaptation. To complete this process, switch of viral haemagglutinin (HA) specificity from human to avian type, mediated by HA mutations, is believed to be a major determinant. Thus it is important to characterize the receptor binding properties of newly emergent viruses to predict their pandemic potential. A biolayer interferometry assay has been developed to quantitate influenza virus binding. This method has allowed us to measure receptor binding changes during the evolutions of H3N2, H5N1, and H7N9 subtypes. Together with the binding assay results, structural analyses of haemagglutinin-receptor complexes revealed multiple mechanisms of receptor binding change. These results highlight the complexity and plasticity of the receptor binding site during influenza virus evolution. Communications (Institute, address, email) Division of Virology, MRC National Institute for Medical Research, Mill Hill, London, UK [email protected] Education BSc University of Bristol PhD University of Bristol Research Interests Virology and structural biology of orthomyxoviruses SELECTED PUBLICATIONS Lin, Y. P.*, Xiong, X.*, Wharton, S. A., Martin, S. R., Coombs, P. J., Vachieri, S. G., Christodoulou, E., Walker, P. A., Liu, J., Skehel, J. J., Gamblin, S. J., Hay, A. J., Daniels, R. S. & McCauley, J. W. 2012. Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin. Proc Natl Acad Sci U S A, 109, 21474-9. *These authors contributed equally to the project. Xiong, X.*, Coombs, P. J.*, Martin, S. R.*, Liu, J., Xiao, H., McCauley, J. W., Locher, K., Walker, P. A., Collins, P. J., Kawaoka, Y., Skehel, J. J. & Gamblin, S. J. 2013. Receptor binding by a ferret-transmissible H5 avian influenza virus. Nature, 497, 392-6. *These authors contributed equally to the project. Xiong, X., Martin, S. R., Haire, L. F., Wharton, S. A., Daniels, R. S., Bennett, M. S., McCauley, J. W., Collins, P. J., Walker, P. A., Skehel, J. J. & Gamblin, S. J. 2013. Receptor binding by an H7N9 influenza virus from humans. Nature, 499, 496-9.