OmniVira

Literature detail

Recent avian H5N1 viruses exhibit increased propensity for acquiring human receptor specificity.

James Stevens1 Ola Blixt Li-Mei Chen Ruben O Donis James C Paulson Ian A Wilson
Affiliations 1 institutions
  1. Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. [email protected]
PMID 18672252 2008 J Mol Biol eng ppublish
PubMed DOI Browse context

Article

Publication summary

Adaptation of avian influenza viruses for replication and transmission in the human host is believed to require mutations in the hemagglutinin glycoprotein (HA) which enable binding to human alpha2-6 sialosides and concomitant reduction in affinity for avian alpha2-3 linked sialosides. Here, we show by glycan microarray analyses that the two mutations responsible for such specificity changes in 1957 H2N2 and 1968 H3N2 pandemic viruses, when inserted into recombinant HAs or intact viruses of some recent avian H5N1 isolates (clade 2.2), impart such attributes. This propensity to adapt to human receptors is primarily dependent on arginine at position 193 within the receptor-binding site, as well as loss of a vicinal glycosylation site. Widespread occurrence of these susceptible H5N1 clade 2.2 influenza strains has already occurred in Europe, the Middle East, and Africa. Thus, these avian strains should be considered high-risk, because of their significantly lower threshold for acquiring human receptor specificity and, therefore, warrant increased surveillance and further study.

Animals Birds Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza A Virus, H5N1 Subtype Insecta Ligands Models, Molecular Mutation Phylogeny Polysaccharides Protein Structure, Secondary Receptors, Virus Virus Diseases

Structured evidence records

Evidence records

3 total
Genomic Evolution 1 records
Genomic Evolution Extraction confidence 0.70
Key finding

Mutations in the HA gene, including arginine at position 193 and loss of an adjacent glycosylation site, were found to confer human receptor binding capability to avian H5N1 clade 2.2 viruses, showing evolutionary potential toward human adaptation.

Virus
IAV H5N1
Host
Aves
Location
Not specified
Supporting text

Here, we show by glycan microarray analyses that the two mutations responsible for such specificity changes in 1957 H2N2 and 1968 H3N2 pandemic viruses, when inserted into recombinant HAs or intact viruses of some recent avian H5N1 isolates (clade 2.2), impart such attributes. This propensity to adapt to human receptors is primarily dependent on arginine at position 193 within the receptor-binding site, as well as loss of a vicinal glycosylation site.

Genes or proteins
HA
Analysis methods
mutation analysis; comparative analysis
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Hemagglutinin mutations in recent avian H5N1 viruses confer human-type receptor binding, with Arg193 and loss of a neighboring glycosylation site promoting adaptation to human α2-6 sialoside receptors.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

We show by glycan microarray analyses that the two mutations responsible for such specificity changes in 1957 H2N2 and 1968 H3N2 pandemic viruses, when inserted into recombinant HAs or intact viruses of some recent avian H5N1 isolates (clade 2.2), impart such attributes. This propensity to adapt to human receptors is primarily dependent on arginine at position 193 within the receptor-binding site, as well as loss of a vicinal glycosylation site.

Genes or proteins
hemagglutinin; HA
Receptors
human α2-6 sialoside; avian α2-3 linked sialoside
Mutations
Arg193; loss of glycosylation site
Mechanism types
receptor_binding; host_range; molecular_adaptation
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.95
Key finding

Avian H5N1 influenza viruses acquire human-type alpha2-6 sialoside receptor binding through HA mutations, increasing human receptor specificity while reducing avian receptor affinity.

Virus
IAV H5N1
Location
Not specified
Supporting text

Adaptation of avian influenza viruses for replication and transmission in the human host is believed to require mutations in the hemagglutinin glycoprotein (HA) which enable binding to human alpha2-6 sialosides and concomitant reduction in affinity for avian alpha2-3 linked sialosides. Here, we show by glycan microarray analyses that the two mutations responsible for such specificity changes, when inserted into recombinant HAs or intact viruses of recent avian H5N1 isolates, impart such attributes.

Method
glycan microarray analysis
Receptors
human alpha2-6 sialoside