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Access to the article is free, however registration and sign-in are required. The deadly Spanish flu pandemic of 1918 killed more people than World War I. Given concerns over newly emerging infections, there is much interest in learning why the 1918 influenza virus was so virulent. In his Perspective, Holmes discusses two recent studies that resolve the structures of the hemagglutinin proteins of the 1918 virus and of other related strains (Gamblin et al.; Stevens et al.). As Holmes explains, the structures reveal that the 1918 virus hemagglutinin retains many of the characteristics of its avian ancestors that may have imbued this virus with its ferocious pathogenicity.
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