OmniVira

Enhanced human receptor binding by H5 haemagglutinins.

Xiaoli Xiong1 Haixia Xiao1 Stephen R Martin1 Peter J Coombs1 Junfeng Liu1 Patrick J Collins1 Sebastien G Vachieri1 Philip A Walker1 Yi Pu Lin1 John W McCauley1 Steven J Gamblin1 John J Skehel2
Affiliations 2 institutions
  1. MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
  2. MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Electronic address: [email protected].
PMID24889237 DOI10.1016/j.virol.2014.03.008 Year2014 Journal Virology Languageeng Statusppublish

Abstract

Mutant H5N1 influenza viruses have been isolated from humans that have increased human receptor avidity. We have compared the receptor binding properties of these mutants with those of wild-type viruses, and determined the structures of their haemagglutinins in complex with receptor analogues. Mutants from Vietnam bind tighter to human receptor by acquiring basic residues near the receptor binding site. They bind more weakly to avian receptor because they lack specific interactions between Asn-186 and Gln-226. In contrast, a double mutant, Δ133/Ile155Thr, isolated in Egypt has greater avidity for human receptor while retaining wild-type avidity for avian receptor. Despite these increases in human receptor binding, none of the mutants prefers human receptor, unlike aerosol transmissible H5N1 viruses. Nevertheless, mutants with high avidity for both human and avian receptors may be intermediates in the evolution of H5N1 viruses that could infect both humans and poultry.

Supporting text Virus Host Location
Avian influenza virus 59 Biolayer interferometry 2 H5N1 influenza virus 4 Haemagglutinin 3 Haemagglutinin crystal structure 1 Receptor binding 30 Receptor specificity 4 Animals 1948 Birds 212 Crystallography, X-Ray 32 Hemagglutinin Glycoproteins, Influenza Virus 180 Humans 1440 Influenza A Virus, H5N1 Subtype 300 Influenza in Birds 341 Influenza, Human 286 Models, Molecular 99 Protein Binding 193 Protein Conformation 44 Receptors, Virus 204 hemagglutinin, avian influenza A virus 26

Evidence records

2 total
Functional Mechanism
2 records · 1 evidence types
Evidence type Molecular Adaptation
2 records
OVE1731 Molecular Adaptation
Key finding

H5N1 mutants from Vietnam acquired basic residues near the receptor binding site, enhancing binding to the human receptor and weakening binding to the avian receptor by loss of Asn-186 and Gln-226 interactions.

Virus
Influenza A virus H5N1
Host
Not specified
Location
Not specified
Supporting text

Mutants from Vietnam bind tighter to human receptor by acquiring basic residues near the receptor binding site. They bind more weakly to avian receptor because they lack specific interactions between Asn-186 and Gln-226.

Genes or proteins
haemagglutinin
Receptors
human receptor | avian receptor
Mutations
basic residues near receptor binding site | loss of Asn-186 | loss of Gln-226 interactions
Mechanism types
receptor binding | host-range expansion
OVE1732 Molecular Adaptation
Key finding

An H5N1 double mutant Δ133/Ile155Thr isolated in Egypt showed increased avidity for the human receptor while maintaining wild-type avidity for the avian receptor.

Virus
Influenza A virus H5N1
Host
Not specified
Location
Not specified
Supporting text

In contrast, a double mutant, Δ133/Ile155Thr, isolated in Egypt has greater avidity for human receptor while retaining wild-type avidity for avian receptor.

Genes or proteins
haemagglutinin
Receptors
human receptor | avian receptor
Mutations
Δ133 | Ile155Thr
Mechanism types
receptor binding | host-range expansion