Structural analysis of the hemagglutinin from the recent 2013 H7N9 influenza virus

tions. The newly emerging H7N9 viruses constitute an obvious public health concern because of the apparent severity of this outbreak. Here we focus on the hemagglutinins (HAs) of these viruses and assess their receptor binding phenotype in relation to previous HAs studied. Glycanmicroarray and kinetic analyses of recombinant A(H7N9) HAs were performed to compare the receptor binding profile of wild-type receptor binding site variants at position 217, a residue analogous to one of two positions known to switch avian to human receptor preference in H2N2 and H3N2 viruses. Two recombinant A(H7N9) HAs were structur-ally characterized, and a mutational study of the receptor binding site was performed to analyze important residues that can af-fect receptor preference and affinity. Results highlight a weak human receptor preference of the H7N9HAs, suggesting that these viruses require further adaptation in order to adapt fully to humans. Annually, influenza viruses pose a serious global public healthrisk as they can infect up to 20 % of the human population. In the United States alone, estimates of influenza-associated deaths range from 3,000 to 49,000 per annum (1). In the last century, three influenza virus subtypes have successfully adapted to the human population, causing four pandemics, H1N1 in 1918 and most recently 2009, H2N2 in 1957, and H3N2 in 1968 (2–4). Other subtypes are prevalent in domestic poultry in certain part