Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses.
Yi Shi1
Wei Zhang
Fei Wang
Jianxun Qi
Ying Wu
Hao Song
Feng Gao
Yuhai Bi
Yanfang Zhang
Zheng Fan
Chengfeng Qin
Honglei Sun
Jinhua Liu
Joel Haywood
Wenjun Liu
Weimin Gong
Dayan Wang
Yuelong Shu
Yu Wang
Jinghua Yan
George F Gao
Affiliations1 institutions
Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
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 Gln(226)) and A/Anhui/1/2013 (AH-H7N9) (containing the mammalian-signature residue Leu(226)). 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 (Leu(226) → 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.
AnimalsBirdsCrystallography, X-RayGlycineHemagglutinin Glycoproteins, Influenza VirusHumansInfluenza A virusInfluenza in BirdsInfluenza, HumanProtein ConformationReceptors, Cell Surfacehemagglutinin, avian influenza A virus
Structured evidence records
Evidence records
3 total
Molecular Adaptation1 records
Molecular AdaptationExtraction confidence 0.95
Key finding
The H7N9 influenza virus hemagglutinin with Leu226 shows binding to both avian and human receptor analogs, demonstrating molecular adaptation enabling human receptor recognition.
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 (Leu(226) → Gln) was found to exhibit dual receptor-binding property, indicating that other amino acid substitutions contribute to the receptor-binding switch.
Genes or proteins
HA; hemagglutinin
Receptors
avian receptor analog; human receptor analog
Mutations
Leu226; Gln226
Mechanism types
receptor_binding; host_adaptation
Receptor Usage1 records
Receptor UsageExtraction confidence 1.00
Key finding
Hemagglutinin from the SH-H7N9 influenza virus binds avian-type receptors, while that from the AH-H7N9 influenza virus recognizes both avian and human receptor analogs, indicating dual receptor usage linked to residue 226 variation.
