Literature detail

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

MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK.
MRC National Institute for Medical Research, The Ridgeway, Mill Hill, London NW7 1AA, UK. Electronic address: [email protected].

PMID 24889237 2014 Virology eng ppublish

PubMed DOI Browse context

Article

Publication summary

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.

Avian influenza virus Biolayer interferometry H5N1 influenza virus Haemagglutinin Haemagglutinin crystal structure Receptor binding Receptor specificity Animals Birds Crystallography, X-Ray Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza A Virus, H5N1 Subtype Influenza in Birds Influenza, Human Models, Molecular Protein Binding Protein Conformation

Structured evidence records

Evidence records

5 total

Molecular Adaptation 2 records

Molecular Adaptation Extraction confidence 0.95

Key finding

Vietnamese H5N1 haemagglutinin mutants achieved stronger human receptor binding through acquisition of basic residues near the receptor binding site and loss of avian receptor interactions at Asn-186 and Gln-226.

Virus

Host

Location

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: Asn-186; Gln-226
Mechanism types: receptor_binding; host_range_adaptation

Molecular Adaptation Extraction confidence 0.95

Key finding

An Egyptian H5N1 haemagglutinin double mutant (Δ133/Ile155Thr) showed enhanced binding to human receptor without loss of avian receptor affinity, suggesting adaptation toward dual host receptor recognition.

Virus

Host

Location

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_adaptation

Receptor Usage 2 records

Receptor Usage Extraction confidence 1.00

Key finding

Vietnam-derived H5N1 influenza virus mutants acquire basic residues near the haemagglutinin receptor binding site that enhance binding to human receptors and reduce affinity for avian receptors.

Virus

Host

Location

Supporting text

Method: structural analysis; receptor binding assay
Receptors: human receptor

Receptor Usage Extraction confidence 1.00

Key finding

An H5N1 double mutant Δ133/Ile155Thr from Egypt shows increased binding to human receptors while maintaining wild-type binding to avian receptors.

Virus

Host

Location

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.

Method: receptor binding assay
Receptors: human receptor

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.80

Key finding

Structural and molecular comparison of mutant H5N1 haemagglutinins revealed amino acid substitutions near the receptor-binding site that enhance human receptor binding, indicating evolutionary changes linked to host adaptation.

Virus

Host

Location

Supporting text

Genes or proteins: haemagglutinin
Analysis methods: structural analysis; comparative evolutionary analysis

Citation context

References

34 references

Reference network

Force-directed citation graph. OmniVira-indexed references are prioritized and recursively expanded up to three steps.

260 nodes · 422 links · capped

Drag nodes to explore citation neighborhoods


PMID 22056389	in vitro evolution of H5N1 avian influenza virus toward human-type receptor specificity	Chen	2012
PMID 20057044	MolProbity: all-atom structure validation for macromolecular crystallography	Chen	2010
PMID 20392847	, van Riel D	Chutinimitkul	2010
PMID 7975212	Receptor specificity in human, avian, and equine H2 and H3 influenza virus isolates	Connor	1994
-	The genetic drift of Indonesian Avian Influenza A H5N1 viruses during 2003–2008	Dharmayanti N.L.P.I	2011
PMID 9185585	Binding of the influenza A virus to cell-surface receptors: structures of five hemagglutinin-sialyloligosaccharide complexes determined by X-ray crystallography	Eisen	1997
PMID 20383002	Features and development of coot	Emsley	2010
PMID 16369096	Scaling and assessment of data quality	Evans	2006
PMID 16226289 In OmniVira	Evolution of the receptor binding phenotype of influenza A (H5) viruses.	Gambaryan	2006
PMID 14764886	The structure and receptor binding properties of the 1918 influenza hemagglutinin	Gamblin	2004
PMID 23577628	Human infection with a novel avian-origin influenza A (H7N9) virus. N. Engl	Gao	2013
PMID 22723413 In OmniVira	Airborne transmission of influenza A/H5N1 virus between ferrets.	Herfst	2012
PMID 10801978	A DNA transfection system for generation of influenza A virus from eight plasmids	Hoffmann	2000
PMID 22722205 In OmniVira	Experimental adaptation of an influenza H5 HA confers respiratory droplet transmission to a reassortant H5 HA/H1N1 virus in ferrets.	Imai	2012
PMID 20124692	Acta Crystallogr	Kabsch	2010
-	Processing diffraction data with MOSFLM	Leslie	2007
PMID 10920197	Avian-to-human transmission of H9N2 subtype influenza A viruses: relationship between H9N2 and H5N1 human isolates	Lin	2000
PMID 23236176	Evolution of the receptor binding properties of the influenza A(H3N2) hemagglutinin	Lin	2012
PMID 19805083	Structures of receptor complexes formed by hemagglutinins from the Asian Influenza pandemic of 1957	Liu	2009
PMID 10954551	Early alterations of the receptor-binding properties of H1, H2, and H3 Avian Influenza virus hemagglutinins after their introduction into mammals	Matrosovich	2000
PMID 19461840	Phaser crystallographic software	McCoy	2007
PMID 15299926	Refinement of macromolecular structures by the maximum-likelihood method	Murshudov	1997
PMID 23166487	Egyptian H5N1 influenza viruses-cause for concern? PLoS Pathog. 2012;8:e1002932	Neumann	2012
PMID 6191220	Single amino acid substitutions in influenza haemagglutinin change receptor binding specificity	Rogers	1983
PMID 4998414	The polypeptide composition of influenza A viruses	Skehel	1971
PMID 21637809 In OmniVira	Acquisition of human-type receptor binding specificity by new H5N1 influenza virus sublineages during their emergence in birds in Egypt.	Watanabe	2011
-	Cumulative Number of Confirmed Human Cases of Avian Influenza A (H5N1) reported to WHO	WHO	2013
PMID 21460441	Overview of the CCP4 suite and current developments	Winn	2011
PMID 15378048	From lethal virus to life-saving vaccine: developing inactivated vaccines for pandemic influenza	Wood	2004
PMID 23615615 In OmniVira	Receptor binding by a ferret-transmissible H5 avian influenza virus.	Xiong	2013
PMID 23787694 In OmniVira	Receptor binding by an H7N9 influenza virus from humans.	Xiong	2013
PMID 22072785	Structural characterization of the hemagglutinin receptor specificity from the 2009 H1N1 influenza pandemic	Xu	2012
PMID 17108965 In OmniVira	Haemagglutinin mutations responsible for the binding of H5N1 influenza A viruses to human-type receptors.	Yamada	2006
PMID 23641058 In OmniVira	An airborne transmissible avian influenza H5 hemagglutinin seen at the atomic level.	Zhang	2013

Evidence overview

Evidence 5

Types 3

Virus 1

Host 1

Evidence types

Molecular Adaptation 2 Receptor Usage 2 Genomic Evolution 1

Linked entities

Viruses

Hosts

Locations

Publication metadata

Journal: Virology
Volume / Issue / Pages: 456-457 / 100 / 179-87
ISSN: 1096-0341
Journal country: United States
DOI: 10.1016/j.virol.2014.03.008