[This is the publication of the "Cell" which the article I posted at the blog below is referring to]
Cell, 06 June 2013
10.1016/j.cell.2013.05.035
Abstract
Authors
Kannan Tharakaraman, Rahul Raman, Karthik Viswanathan, Nathan W. Stebbins, Akila Jayaraman, Arvind Krishnan, V. Sasisekharan, Ram Sasisekharan
See Affiliations
See Affiliations- Highlights
- Hallmark mutations do not switch receptor preference of recent H5 strains
- Structural comparison of H5 and H2 hemagglutinin receptor complexes
- Determination of key H5Nl receptor-binding features needed for quantitative switch
- Recent strains may require a single base pair change to switch receptor preference
Summary
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.
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