OmniVira

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
Affiliations 1 institutions
  1. Research Network of Immunity and Health, Beijing Institutes of Life Science, Chinese Academy of Sciences, Beijing, China.
PMID24009358 DOI10.1126/science.1242917 Year2013 Journal Science (New York, N.Y.) Science Languageeng Statusppublish

Abstract

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.

Supporting text Virus Host Location
Animals 1948 Birds 212 Crystallography, X-Ray 32 Glycine 1 Hemagglutinin Glycoproteins, Influenza Virus 180 Humans 1440 Influenza A virus 186 Influenza in Birds 341 Influenza, Human 286 Protein Conformation 44 Receptors, Cell Surface 28 hemagglutinin, avian influenza A virus 26

Evidence records

3 total
Functional Mechanism
3 records · 2 evidence types
Evidence type Receptor Usage
2 records
OVE1561 Receptor Usage
Key finding

A/Shanghai/1/2013 (SH-H7N9) hemagglutinin preferentially binds avian receptor analogs, while A/Anhui/1/2013 (AH-H7N9) hemagglutinin binds both avian and human receptor analogs.

Virus
Influenza A virus H7N9
Host
birds Aves Experimental system human Homo sapiens Experimental system
Location
Not specified
Supporting text

We found that SH-H7N9 HA preferentially binds the avian receptor analog, whereas AH-H7N9 HA binds both avian and human receptor analogs.

Method
receptor-binding assay
Receptors
avian receptor analog | human receptor analog
OVE1562 Receptor Usage
Key finding

Structural complexes of AH-H7N9 hemagglutinin demonstrate binding to human receptor analogs while retaining avian receptor-binding capacity.

Virus
Influenza A virus H7N9
Host
birds Aves Experimental system human Homo sapiens Experimental system
Location
Not specified
Supporting text

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.

Method
X-ray crystallography | structural complex analysis
Receptors
avian receptor analog | human receptor analog
Evidence type Molecular Adaptation
1 records
OVE1563 Molecular Adaptation
Key finding

A Leu226→Gln substitution in the hemagglutinin of A/Anhui/1/2013 (AH-H7N9) contributes to a receptor-binding switch enabling dual binding to avian and human receptor analogs.

Virus
Influenza A virus H7N9
Host
Not specified
Location
Not specified
Supporting text

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
hemagglutinin | HA
Receptors
avian receptor analog | human receptor analog
Mutations
Leu(226)→Gln
Mechanism types
receptor binding | receptor usage | host-range expansion