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Changes in the hemagglutinin of H5N1 viruses during human infection - Influence on receptor binding
- Source :
- RUNA. Repositorio da Consellería de Sanidade e Sergas, Servizo Galego de Saúde (SERGAS), Virology, 447(1-2), 326-337. Academic Press Inc., Virology
- Publication Year :
- 2016
-
Abstract
- 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.<br />Highlights • Changes in receptor binding of HA during H5N1 human infection were identified. • Single A134V and L151F substitutions caused reduced affinity for avian receptors. • Glycan array analyses were used to identify changes in receptor binding specificity. • Structural basis for altered receptor binding was examined by X-ray crystallography.
- Subjects :
- H5N1 influenza infection
Biolayer interferometry
Protein Conformation
Hemagglutinin Glycoproteins, Influenza Virus
Plasma protein binding
Acoplamiento Viral
Crystallography, X-Ray
medicine.disease_cause
Poultry
Protein structure
Mutación Missense
Hemagglutinin
Receptor
0303 health sciences
biology
Pyrosequencing
Hemagglutinin X-ray crystal structure
Phenotype
3. Good health
Receptor specificity
Synthetic sialylglycopolymers
RNA, Viral
Receptors, Virus
Protein Binding
Viral protein
Mutation, Missense
Virus Attachment
Hemagglutinin (influenza)
Proteínas Mutantes
Article
Virus
03 medical and health sciences
Virology
Influenza, Human
medicine
Animals
Humans
Hemagglutination assays
030304 developmental biology
Carbohydrate microarray
Influenza A Virus, H5N1 Subtype
030306 microbiology
Gripe Aviar
Sequence Analysis, DNA
Cristalografía por Rayos X
Glicoproteínas Hemaglutininas del Virus de la Influenza
Subtipo H5N1 del Virus de la Influenza A
Influenza A virus subtype H5N1
Influenza in Birds
biology.protein
Receptor binding
Mutant Proteins
Subjects
Details
- Language :
- English
- ISSN :
- 00426822
- Database :
- OpenAIRE
- Journal :
- RUNA. Repositorio da Consellería de Sanidade e Sergas, Servizo Galego de Saúde (SERGAS), Virology, 447(1-2), 326-337. Academic Press Inc., Virology
- Accession number :
- edsair.doi.dedup.....2606a1d216ab72da7642929cdfbc9b73