Structures and Receptor Binding of Hemagglutinins from Human-Infecting H7N9 Influenza Viruses

• Published in: Science (American Association for the Advancement of Science) Vol. 342; no. 6155; pp. 243 - 247
• Main Authors: Shi, Yi, Zhang, Wei, Wang, Fei, Qi, Jianxun, Wu, Ying, Song, Hao, Gao, Feng, Bi, Yuhai, Zhang, Yanfang, Fan, Zheng, Qin, Chengfeng, Sun, Honglei, Liu, Jinhua, Haywood, Joel, Liu, Wenjun, Gong, Weimin, Wang, Dayan, Shu, Yuelong, Wang, Yu, Yan, Jinghua, Gao, George F.
• Format: Journal Article
• Language: English
• Published: United States American Association for the Advancement of Science 11.10.2013; The American Association for the Advancement of Science
• Subjects: Affinity; Amino acids; Animals; Avian flu; Binding; Birds; Crystallography, X-Ray; Glycine - chemistry; Glycine - genetics; Glycine - metabolism; Hemagglutinin Glycoproteins, Influenza Virus - chemistry; Hemagglutinin Glycoproteins, Influenza Virus - metabolism; Human; Humans; Hydroxyapatite; Influenza; Influenza A virus - metabolism; Influenza in Birds - virology; Influenza, Human - virology; Protein Conformation; Receptors; Receptors, Cell Surface - chemistry; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Virology; Viruses
• ISSN: 0036-8075; 1095-9203
• DOI: 10.1126/science.1242917

An avian-origin human-infecting influenza (H7N9) virus was recently identified in China. We have evaluated the viral hemagglutinin (HA) receptor-binding properties of two human H7N9 isolates, A/Shanghai/1/2013 (SH-H7N9) (containing the avian-signature residue Gln²²⁶) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature residue Leu²²⁶). We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas AH-H7N9 HA binds both avian and human receptor analogs. Furthermore, an AH-H7N9 mutant HA (Leu²²⁶ → Gln) was found to exhibit dual receptor-binding property, indicating that other amino acid substitutions contribute to the receptor-binding switch. The structures of SH-H7N9 HA, AH-H7N9 HA, and its mutant in complex with either avian or human receptor analogs show how AH-H7N9 can bind human receptors while still retaining the avian receptor-binding property.