OmniVira

Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity.

Kannan Tharakaraman1 Rahul Raman Karthik Viswanathan Nathan W Stebbins Akila Jayaraman Arvind Krishnan V Sasisekharan Ram Sasisekharan
Affiliations 1 institutions
  1. Department of Biological Engineering, Koch Institute of Integrative Cancer Research, Infectious Diseases Interdisciplinary Research Group, Singapore-MIT Alliance for Research and Technology, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA.
PMID23746829 DOI10.1016/j.cell.2013.05.035 Year2013 Journal Cell Languageeng Statusppublish

Abstract

Of the factors governing human-to-human transmission of the highly pathogenic avian-adapted H5N1 virus, the most critical is the acquisition of mutations on the viral hemagglutinin (HA) to "quantitatively switch" its binding from avian to human glycan receptors. Here, we describe a structural framework that outlines a necessary set of H5 HA receptor-binding site (RBS) features required for the H5 HA to quantitatively switch its preference to human receptors. We show here that the same RBS HA mutations that lead to aerosol transmission of A/Vietnam/1203/04 and A/Indonesia/5/05 viruses, when introduced in currently circulating H5N1, do not lead to a quantitative switch in receptor preference. We demonstrate that HAs from circulating clades require as few as a single base pair mutation to quantitatively switch their binding to human receptors. The mutations identified by this study can be used to monitor the emergence of strains having human-to-human transmission potential.

Supporting text Virus Host Location
Amino Acid Sequence 128 Animals 1948 Birds 212 Evolution, Molecular 176 Hemagglutinin Glycoproteins, Influenza Virus 180 Host Specificity 132 Humans 1440 Influenza A Virus, H5N1 Subtype 300 Influenza in Birds 341 Influenza, Human 286 Models, Molecular 99 Molecular Sequence Data 160 Mutation 209 N-Acetylneuraminic Acid 25 Phylogeny 805 Receptors, Virus 204 Sequence Alignment 51 hemagglutinin, avian influenza A virus 26

Evidence records

2 total
Functional Mechanism
2 records · 1 evidence types
Evidence type Molecular Adaptation
2 records
OVE1452 Molecular Adaptation
Key finding

HA receptor-binding site mutations that confer aerosol transmission in A/Vietnam/1203/04 and A/Indonesia/5/05 affect receptor binding and adaptation but do not switch receptor preference when introduced into circulating H5N1 viruses.

Virus
Influenza A virus H5N1
Host
Not specified
Location
Not specified
Supporting text

We show here that the same RBS HA mutations that lead to aerosol transmission of A/Vietnam/1203/04 and A/Indonesia/5/05 viruses, when introduced in currently circulating H5N1, do not lead to a quantitative switch in receptor preference.

Genes or proteins
HA | receptor-binding site (RBS)
Receptors
avian glycan receptors | human glycan receptors
Mechanism types
receptor binding | receptor usage | host-range expansion | transmission fitness
OVE1453 Molecular Adaptation
Key finding

H5N1 hemagglutinin from circulating clades can switch binding to human receptors with as few as a single base pair mutation, indicating potential adaptation toward human receptor usage.

Virus
Influenza A virus H5N1
Host
Not specified
Location
Not specified
Supporting text

Of the factors governing human-to-human transmission of the highly pathogenic avian-adapted H5N1 virus, the most critical is the acquisition of mutations on the viral hemagglutinin (HA) to "quantitatively switch" its binding from avian to human glycan receptors. We demonstrate that HAs from circulating clades require as few as a single base pair mutation to quantitatively switch their binding to human receptors.

Genes or proteins
HA
Receptors
human receptors
Mutations
single base pair mutation
Mechanism types
receptor binding | receptor usage | host-range expansion