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Literature detail

Immunization by avian H5 influenza hemagglutinin mutants with altered receptor binding specificity.

Zhi-Yong Yang1 Chih-Jen Wei Wing-Pui Kong Lan Wu Ling Xu David F Smith Gary J Nabel
Affiliations 1 institutions
  1. Vaccine Research Center, National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Building 40, Room 4502, Mailstop Code MSC-3005, 40 Convent Drive, Bethesda, MD 20892, USA.
PMID 17690300 2007 Science eng ppublish
PubMed DOI Browse context

Article

Publication summary

Influenza virus entry is mediated by the receptor binding domain (RBD) of its spike, the hemagglutinin (HA). Adaptation of avian viruses to humans is associated with HA specificity for alpha2,6- rather than alpha2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing alpha2,3- or increasing alpha2,6-SA recognition. RBD mutants were used to develop vaccines and monoclonal antibodies that neutralized new variants. Structure-based modification of HA specificity can guide the development of preemptive vaccines and therapeutic monoclonal antibodies that can be evaluated before the emergence of human-adapted H5N1 strains.

Mutation Animals Antibodies, Monoclonal Antibodies, Viral Carbohydrate Conformation Cell Line Female Genes, Viral Hemagglutination Inhibition Tests Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza A Virus, H5N1 Subtype Influenza Vaccines Mice Mice, Inbred BALB C Molecular Sequence Data Neutralization Tests Receptors, Virus

Structured evidence records

Evidence records

2 total
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Mutations in the H5N1 hemagglutinin modify receptor binding specificity from avian-type alpha2,3-linked to human-type alpha2,6-linked sialic acid, demonstrating molecular adaptation relevant to human infection potential.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

We define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for sialic acid either by decreasing alpha2,3- or increasing alpha2,6-SA recognition.

Genes or proteins
HA
Receptors
alpha2,3-linked sialic acid; alpha2,6-linked sialic acid
Mechanism types
receptor_binding
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.95
Key finding

Mutations in the hemagglutinin of avian influenza A H5N1 change receptor binding specificity, reducing affinity for alpha2,3-linked sialic acid and increasing recognition of alpha2,6-linked sialic acid receptors.

Virus
IAV H5N1
Location
Not specified
Supporting text

Adaptation of avian viruses to humans is associated with HA specificity for alpha2,6- rather than alpha2,3-linked sialic acid (SA) receptors. Here, we define mutations in influenza A subtype H5N1 (avian) HA that alter its specificity for SA either by decreasing alpha2,3- or increasing alpha2,6-SA recognition.

Method
structure-based modification
Receptors
sialic acid (SA) receptors