During infection, viruses use hemagglutinin proteins to bind to the cells of hosts. Avian viruses employ a variety of hemagglutinins, numbered H1 through H16. Only H1, H2, and H3 have adapted successfully to the human population, in each case triggering a pandemic. Scripps Research Institute scientists have now determined the structure of an H5 hemagglutinin from a highly pathogenic strain of H5N1 avian influenza virus. In a paper in Science, James Stevens, Ian A. Wilson, and colleagues compare the structure of the protein (shown) with hemagglutinins from other influenza viruses carried by birds and humans, including the virus responsible for the deadly 1918 flu epidemic (published online March 16, dx.doi.org/10.1126/science.1124513). The researchers also analyze the protein's binding specificity. Their results reveal one possible route by which the virus could mutate and switch from a preference for binding to receptors on avian cells to receptors on human cells and thus adapt to the human population.