Receptor-binding preference of mutant HA proteins. (A) Binding of HA proteins to sialylglycopolymers that correspond to influenza virus receptors on avian (α2,3; red) or human (α2,6; blue) cells. H5NAHAΔ/PR8 (a virus that binds to avian-type receptors), K173NAHA/PR8 (a virus that binds to human-type receptors), and the indicated mutant viruses were evaluated for their ability to bind to the avian- or human-type receptor analogs. (B) Binding to human tissue sections (trachea, alveolus). The indicated viruses were labeled with FITC and incubated with the tissue samples. Tracheal cells contain primarily α2,6 (human-type) receptors, whereas alveolar cells contain α2,6 (human-) and α2,3 (avian-type) receptors. PBS, control. A “+” indicates that the HA protein encodes the respective amino acid change(s) in the background of H5HA-N224K+Q226L.