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Mapping of evolution and adaptation of the influenza virus hemagglutinin protein by glycan array cartography

Objective

Influenza viruses belong to the family of Orthomyxoviridae and cause acute viral disease of the respiratory tract. Influenza virus enters the cell via receptor-mediated endocytosis and subsequent fusion with the cell membrane. Influenza virus hemagglutinin (HA) is responsible for these binding and fusion events. HA binds to sialic acid (SA) receptors on the host cell-surface. These SA receptors vary in structures and are species and tissue specific. The preference for a certain SA receptor is influenza virus specific; human and avian influenza viruses prefer (SA)-α2-6-Gal and (SA)-α2-3-Gal terminated structures respectively. Studies on the interactions of glycan binding proteins such as HA have advanced significantly since the development of glycan array technologies. Using this new technology it has been shown that the receptor specificity is more complex than previously recognized and is not solely dependent on the type of glycan sialic-acid linkage, but also involves glycan modifications, such as fucosylation, sulphation, etc. There is a huge potential in the use of glycan arrays in the understanding of receptor specificity, but a major drawback for this technique is the opacity of the array data, making it difficult to interpret the data and compare data of different arrays. We propose to set up glycan array cartography, a novel method for the analysis of glycan array data in clear accessible maps, providing a spatial layout of assay components (virus strains and SA receptors), allowing the precise measurement of distances and directions amongst components. These analyses will build on the expertise of the host institution on antigenic cartography. The glycan array maps will be thoroughly tested and linked to sequence data, classical binding studies, structural modelling, and antigenic cartography. We anticipate that these studies will increase the value of glycan arrays, and help to increase our understanding of receptor specificity of influenza viruses.

Field of science

  • /natural sciences/biological sciences/microbiology/virology

Call for proposal

FP7-PEOPLE-IEF-2008
See other projects for this call

Funding Scheme

MC-IEF - Intra-European Fellowships (IEF)

Coordinator

THE CHANCELLOR MASTERS AND SCHOLARSOF THE UNIVERSITY OF CAMBRIDGE
Address
Trinity Lane The Old Schools
CB2 1TN Cambridge
United Kingdom
Activity type
Higher or Secondary Education Establishments
EU contribution
€ 170 733,61
Administrative Contact
Keith Cann (Mr.)