Structural determinants for naturally evolving H5N1 hemagglutinin to switch its receptor specificity
Kannan Tharakaraman1, Rahul Raman, Karthik Viswanathan
1Department 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.
Cell
|June 11, 2013
Summary
Understanding H5N1 avian flu transmission is key. Specific mutations in the hemagglutinin
Area of Science:
- Virology
- Structural Biology
- Molecular Biology
Background:
- Human-to-human transmission of highly pathogenic avian influenza A virus (H5N1) is a significant public health concern.
- Viral adaptation to human respiratory tract receptors, specifically human glycan receptors, is a critical factor for efficient transmission.
Purpose of the Study:
- To define the structural features of the H5 hemagglutinin (HA) receptor-binding site (RBS) necessary for switching binding preference from avian to human glycan receptors.
- To identify mutations that confer human receptor binding and assess their potential for H5N1 human adaptation.
Main Methods:
- Structural analysis of H5 HA receptor-binding sites.
- Mutagenesis studies to alter HA receptor binding properties.
- Assessment of viral binding to avian and human glycan receptors.
Main Results:
- A structural framework was established for H5 HA mutations enabling a quantitative switch to human receptor binding.
- Previously identified mutations conferring aerosol transmission in older H5N1 strains did not induce a quantitative switch in currently circulating H5N1 strains.
- HAs from circulating H5N1 clades can achieve a quantitative switch to human receptors with as few as a single base pair mutation.
Conclusions:
- The study identifies critical H5 HA RBS features required for human receptor adaptation.
- The findings highlight that mutations conferring human receptor binding can vary among H5N1 clades.
- The identified mutations serve as potential markers for monitoring H5N1 strains with pandemic potential.
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