A Two-Amino Acid Change in the Hemagglutinin of the 1918 Influenza Virus Abolishes Transmission

By T. Tumpey, T. Maines, N. Van Hoeven, L. Glaser, A. Solórzano, C. Pappas, N. Cox, D. Swayne, P. Palese, J. Katz and 1 more. Science, 2007

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Transmission of Influenza Virus in a Mammalian Host Is Increased by PB2 Amino Acids 627K or 627E/701N (2009, background): “Affinity of the viral hemagglutinin (HA) protein for a-2,6 linked sialic acid residues has been shown to be necessary [4] but not sufficient [2,5] to support transmission between ferrets.”
H5N1 and 1918 Pandemic Influenza Virus Infection Results in Early and Excessive Infiltration of Macrophages and Neutrophils in the Lungs of Mice (2008, methodology): “Female BALB/c mice were infected intranasally with either highly pathogenic (HP) or low-pathogenic (LP) influenza viruses (Table 1, Methods) based on known LD50’s and phenotypes of disease in mouse [21] and ferret [18,22] models.”
Influenza Virus Evolution, Host Adaptation and Pandemic Formation (2010, background): “IAV bearing the 1918 HA with different RBD configurations (α2–3, α2–6 and blended α2–3/α2–6 specificities) were all shown to virulent in mice (Qi et al., 2009) and ferrets, but viral constructs with the 1918 HA having only α2–3 specificity did not transmit between ferrets (Tumpey et al., 2007).”