Literature detail

Changes in the hemagglutinin of H5N1 viruses during human infection--influence on receptor binding.

Martin Crusat^1,2 Junfeng Liu Angelina S Palma Robert A Childs Yan Liu Stephen A Wharton Yi Pu Lin Peter J Coombs Stephen R Martin Mikhail Matrosovich Zi Chen David J Stevens Vo Minh Hien Tran Tan Thanh Le Nguyen Truc Nhu Lam Anh Nguyet Do Quang Ha H Rogier van Doorn Tran Tinh Hien Harald S Conradt Makoto Kiso Steve J Gamblin Wengang Chai John J Skehel Alan J Hay Jeremy Farrar Menno D de Jong Ten Feizi

Affiliations 2 institutions

Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.

PMID 24050651 2013 Virology eng ppublish

PubMed DOI Browse context

Article

Publication summary

As avian influenza A(H5N1) viruses continue to circulate in Asia and Africa, global concerns of an imminent pandemic persist. Recent experimental studies suggest that efficient transmission between humans of current H5N1 viruses only requires a few genetic changes. An essential step is alteration of the virus hemagglutinin from preferential binding to avian receptors for the recognition of human receptors present in the upper airway. We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated, possibly reflecting a receptor-binding phenotype intermediate in adaptation to more human-like characteristics. These observations emphasize that evolution in nature of avian H5N1 viruses to efficient binding of human receptors is a complex multistep process.

Biolayer interferometry Carbohydrate microarray H5N1 influenza infection Hemagglutination assays Hemagglutinin Hemagglutinin X-ray crystal structure Pyrosequencing Receptor binding Receptor specificity Synthetic sialylglycopolymers Mutation, Missense Virus Attachment Animals Crystallography, X-Ray Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza A Virus, H5N1 Subtype Influenza in Birds

Structured evidence records

Evidence records

4 total

Genomic Evolution 1 records

Genomic Evolution Extraction confidence 0.75

Key finding

Single amino acid substitutions Ala134Val and Ile151Phe in the hemagglutinin gene of H5N1 viruses arose during human infection, indicating genomic evolution affecting receptor-binding specificity between avian and human receptors.

Virus

Host

Location

Supporting text

We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin. Detailed biological, receptor-binding, and structural analyses revealed reduced binding of the mutated viruses to avian-like receptors, but without commensurate increased binding to the human-like receptors investigated.

Genes or proteins: hemagglutinin
Analysis methods: sequence analysis; structural analysis

Molecular Adaptation 1 records

Molecular Adaptation Extraction confidence 0.95

Key finding

H5N1 viruses infected in humans showed hemagglutinin substitutions Ala134Val and Ile151Phe that reduced avian receptor binding and produced an intermediate phenotype toward human receptor adaptation.

Virus

Host

Location

Supporting text

Genes or proteins: hemagglutinin
Receptors: avian-like receptors; human-like receptors
Mutations: Ala134Val; Ile151Phe
Mechanism types: receptor_binding; host_adaptation

Receptor Usage 1 records

Receptor Usage Extraction confidence 0.95

Key finding

Mutations Ala134Val and Ile151Phe in H5N1 hemagglutinin decreased binding to avian-like receptors without increased binding to human-like receptors, producing an intermediate receptor-binding specificity.

Virus

Host

Location

Supporting text

Method: receptor-binding assay; structural analysis
Receptors: avian-like receptors

Spillover Event 1 records

Spillover Event Extraction confidence 0.90

Key finding

Avian influenza A(H5N1) viruses infected humans, and viral hemagglutinin mutations arose during these human infections, confirming animal-to-human spillover.

Virus

Host

Location

Supporting text

We have identified receptor-binding changes which emerged during H5N1 infection of humans, due to single amino acid substitutions, Ala134Val and Ile151Phe, in the hemagglutinin.

Method: sequencing; receptor-binding analysis; structural analysis
Study design: molecular analysis
Transmission direction: animal-to-human

Citation context

References

49 references

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Evidence overview

Evidence 4

Types 4

Virus 1

Host 2

Evidence types

Genomic Evolution 1 Molecular Adaptation 1 Receptor Usage 1 Spillover Event 1

Linked entities

Viruses

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Publication metadata

Journal: Virology
Volume / Issue / Pages: 447 / 1-2 / 326-37
ISSN: 1096-0341
Journal country: United States
DOI: 10.1016/j.virol.2013.08.010