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Literature detail

Effect of receptor binding domain mutations on receptor binding and transmissibility of avian influenza H5N1 viruses.

Taronna R Maines1 Li-Mei Chen Neal Van Hoeven Terrence M Tumpey Ola Blixt Jessica A Belser Kortney M Gustin Melissa B Pearce Claudia Pappas James Stevens Nancy J Cox James C Paulson Rahul Raman Ram Sasisekharan Jacqueline M Katz Ruben O Donis
Affiliations 1 institutions
  1. Influenza Division, National Center for Immunization and Respiratory Diseases, Centers for Disease Control & Prevention, 1600 Clifton Road, MS-G16, Atlanta, GA 30333, USA.
PMID 21397290 2011 Virology eng ppublish
PubMed DOI Browse context

Article

Publication summary

Although H5N1 influenza viruses have been responsible for hundreds of human infections, these avian influenza viruses have not fully adapted to the human host. The lack of sustained transmission in humans may be due, in part, to their avian-like receptor preference. Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. The impact of these mutations on replication efficiency was assessed in vitro and in vivo. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro and delayed peak virus shedding in ferrets. An improvement in transmission efficiency was not observed with any of the mutants compared to the parental viruses, indicating that alternative molecular changes are required for H5N1 viruses to fully adapt to humans and to acquire pandemic capability.

Mutation Amino Acid Sequence Animals Cell Line Ferrets Hemagglutinin Glycoproteins, Influenza Virus Humans Influenza A Virus, H5N1 Subtype Influenza, Human Male Molecular Sequence Data Protein Binding Protein Structure, Tertiary Receptors, Virus Virus Replication

Structured evidence records

Evidence records

4 total
Host Range Experiment 2 records
Host Range Experiment Extraction confidence 0.90
Key finding

Mutant H5N1 influenza viruses with altered receptor binding domains showed reduced replication in vitro and delayed virus shedding in ferrets, with no improvement in transmission.

Virus
IAV H5N1
Location
Not specified
Supporting text

The impact of these mutations on replication efficiency was assessed in vitro and in vivo. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro and delayed peak virus shedding in ferrets.

Method
experimental infection; replication assay
Experimental system
in vivo animal experiment
Host Range Experiment Extraction confidence 0.90
Key finding

Mutant H5N1 influenza viruses exhibited reduced replication efficiency in vitro despite altered receptor binding preference.

Virus
IAV H5N1
Location
Not specified
Supporting text

The impact of these mutations on replication efficiency was assessed in vitro and in vivo. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro.

Method
replication assay
Experimental system
in vitro cell culture
Molecular Adaptation 1 records
Molecular Adaptation Extraction confidence 0.95
Key finding

Mutations in the hemagglutinin receptor binding domain of H5N1 altered receptor binding specificity but did not improve replication or transmission efficiency, suggesting limited molecular adaptation to human hosts.

Virus
IAV H5N1
Host
Not specified
Location
Not specified
Supporting text

We introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. Certain mutations switched the receptor binding preference of the H5 HA.

Genes or proteins
hemagglutinin; HA
Receptors
receptor binding domain; glycan receptor
Mechanism types
receptor_binding; replication_efficiency; transmission_fitness
Receptor Usage 1 records
Receptor Usage Extraction confidence 0.95
Key finding

Receptor binding domain mutations in H5N1 hemagglutinin switched receptor binding preference but did not improve transmissibility in ferrets.

Virus
IAV H5N1
Location
Not specified
Supporting text

Here, we have introduced receptor binding domain mutations within the hemagglutinin (HA) gene of two H5N1 viruses and evaluated changes in receptor binding specificity by glycan microarray analysis. Although certain mutations switched the receptor binding preference of the H5 HA, the rescued mutant viruses displayed reduced replication in vitro and delayed peak virus shedding in ferrets.

Method
glycan microarray analysis
Receptors
receptor binding domain