Amino Acid Substitutions That Affect Receptor Binding and Stability of the Hemagglutinin of Influenza A/H7N9 Virus.

Eefje J A Schrauwen¹ Mathilde Richard² David F Burke³ Guus F Rimmelzwaan¹ Sander Herfst¹ Ron A M Fouchier¹

Affiliations 3 institutions

Department of Viroscience, Postgraduate School Molecular Medicine, Erasmus MC, Rotterdam, The Netherlands.
Department of Viroscience, Postgraduate School Molecular Medicine, Erasmus MC, Rotterdam, The Netherlands [email protected].
Department of Zoology, University of Cambridge, Cambridge, United Kingdom.

PMID26792744 DOI10.1128/JVI.03052-15 Year2016 Journal Journal of virology J Virol Languageeng Statusepublish

Abstract

Receptor-binding preference and stability of hemagglutinin have been implicated as crucial determinants of airborne transmission of influenza viruses. Here, amino acid substitutions previously identified to affect these traits were tested in the context of an A/H7N9 virus. Some combinations of substitutions, most notably G219S and K58I, resulted in relatively high affinity for α2,6-linked sialic acid receptor and acid and temperature stability. Thus, the hemagglutinin of the A/H7N9 virus may adopt traits associated with airborne transmission.

Supporting text Virus Host Location

Amino Acid Substitution 81 Virus Attachment 55 Cell Line 158 Hemagglutinin Glycoproteins, Influenza Virus 180 Humans 1440 Influenza A Virus, H7N9 Subtype 87 Mutant Proteins 15 Sialic Acids 29 Temperature 7

Evidence records

1 total

Functional Mechanism

1 records · 1 evidence types

Evidence type Molecular Adaptation

1 records

OVE2276 Molecular Adaptation

Key finding

A/H7N9 virus hemagglutinin substitutions G219S and K58I increase affinity for α2,6-linked sialic acid receptors and enhance acid and temperature stability, indicating molecular adaptations associated with airborne transmission.

Virus

Host

Location

Supporting text

Some combinations of substitutions, most notably G219S and K58I, resulted in relatively high affinity for α2,6-linked sialic acid receptor and acid and temperature stability. Thus, the hemagglutinin of the A/H7N9 virus may adopt traits associated with airborne transmission.

Genes or proteins: hemagglutinin
Receptors: α2,6-linked sialic acid receptor
Mutations: G219S | K58I
Mechanism types: receptor binding | host-range expansion | transmission fitness

References

26 references

Reference network

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

260 nodes · 560 links · capped

Drag nodes to explore citation neighborhoods


-	2015	WHO. 2015. http://www.who.int/influenza/	2015
PMID 23842494	2013. Characterization of H7N9 influenza A viruses isolated from humans	Watanabe	2013
PMID 24009358 In OmniVira	Structures and receptor binding of hemagglutinins from human-infecting H7N9 influenza viruses.	Shi	2013
PMID 25391151	2014. A recommended numbering scheme for influenza A HA subtypes	Burke	2014
PMID 23842497 In OmniVira	Pathogenesis and transmission of avian influenza A (H7N9) virus in ferrets and mice.	Belser	2013
PMID 23925116 In OmniVira	Limited airborne transmission of H7N9 influenza A virus between ferrets.	Richard	2013
PMID 23990570	2014. Novel avian-origin human influenza A(H7N9) can be transmitted between ferrets via respiratory droplets	Xu	2014
PMID 23868922	2013. H7N9 influenza viruses are transmissible in ferrets by respiratory droplet	Zhang	2013
PMID 23704376	2013. Infectivity, transmission, and pathology of human-isolated H7N9 influenza virus in ferrets and pigs	Zhu	2013
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 24725402	2014. Identification, characterization, and natural selection of mutations driving airborne transmission of A/H5N1 virus	Linster	2014
PMID 24027325 In OmniVira	Structural analysis of the hemagglutinin from the recent 2013 H7N9 influenza virus.	Yang	2013
PMID 23746830 In OmniVira	Glycan receptor binding of the influenza A virus H7N9 hemagglutinin.	Tharakaraman	2013
PMID 15163504	2004. Efficient generation and growth of influenza virus A/PR/8/34 from eight cDNA fragments	de Wit	2004
PMID 24311689	2013. Preferential recognition of avian-like receptors in human influenza A H7N9 viruses	Xu	2013
PMID 24162312 In OmniVira	Adaptation of novel H7N9 influenza A virus to human receptors.	Dortmans	2013
PMID 23459660	2013. Influenza HA subtypes demonstrate divergent phenotypes for cleavage activation and pH of fusion: implications for host range and adaptation	Galloway	2013
PMID 24173215 In OmniVira	Hemagglutinin receptor specificity and structural analyses of respiratory droplet-transmissible H5N1 viruses.	de Vries	2014
PMID 22723413 In OmniVira	Airborne transmission of influenza A/H5N1 virus between ferrets.	Herfst	2012
PMID 25187542	2014. A histidine residue of the influenza virus hemagglutinin controls the pH dependence of the conformational change mediating membrane fusion	Mair	2014
PMID 17341496	2007. Andante: reducing side-chain rotamer search space during comparative modeling using environment-specific substitution probabilities	Smith	2007
PMID 23449784 In OmniVira	The pH of activation of the hemagglutinin protein regulates H5N1 influenza virus replication and pathogenesis in mice.	Zaraket	2013
PMID 1763066	1991. Amantadine selection of a mutant influenza virus containing an acid-stable hemagglutinin glycoprotein—evidence for virus-specific regulation of the pH of glycoprotein transport vesicles	Steinhauer	1991
PMID 21490925	2011. Single HA2 mutation increases the infectivity and immunogenicity of a live attenuated H5N1 intranasal influenza vaccine candidate lacking NS1	Krenn	2011
PMID 23486663 In OmniVira	Mutations in haemagglutinin that affect receptor binding and pH stability increase replication of a PR8 influenza virus with H5 HA in the upper respiratory tract of ferrets and may contribute to transmissibility.	Shelton	2013
PMID 23824818 In OmniVira	Increased acid stability of the hemagglutinin protein enhances H5N1 influenza virus growth in the upper respiratory tract but is insufficient for transmission in ferrets.	Zaraket	2013

Evidence overview

Evidence 1

Categories 1

Types 1

Virus 1

Host 0

Country 0

Evidence categories

Linked entities

Viruses

Hosts

No standardized host entity.

Locations

Publication metadata

Journal: Journal of virology
Volume / Issue / Pages: 90 / 7 / 3794-9
ISSN: 1098-5514
Journal country: United States
DOI: 10.1128/JVI.03052-15