276223 Single-Particle Assay for Characterizing the Binding Kinetics of X31 Influenza Virus and the Efficacy of Antiviral Compounds

Wednesday, October 31, 2012
Hall B (Convention Center )
Donald Lee, Chemical Engineering, Cornell, Ithaca, NY and Susan Daniel, Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY

Influenza viruses must bind to their target cell long enough to be internalized by the cell through endocytosis. The duration of binding is determined by the interaction between hemagglutinin proteins (HA) on the virus and the sialic acid receptor (SA) in the target bilayer. Determining the relationship between the receptor molecule structures and their binding duration time with each virus particle can provide new insight towards understanding factors that affect the binding avidity and the tropism of a virus. In addition, this research could aid the development of antiviral compounds that inhibit virus binding and the development of sensors that can identify the target receptor of a new virus strain. Using TIRF microscopy, the binding residence time of individual virus particles with receptors embedded in a supported lipid bilayer has been determined, and the binding time distribution of X31 (H3N2) influenza viruses with alpha2-3 linked sialic acid shows multiple peaks. These peaks suggest that some residence times occur more frequently than others, which may reflect the discrete number of contact points formed between the HA proteins and receptor molecules. This level of detail was not achievable before using standard surface plasmon resonance techniques, which tend to average out these fine details. Further testing shows that GM1 (1 SA per lipid molecule) has shorter binding times than Gd1a (2 SA per lipid molecule), despite the fact that both molecules have the same alpha2-3 linked SA groups. Gd1a may be increasing binding times by increasing the probability of forming more contacts per virus particle. The binding avidity of a virus to receptors has mainly been attributed to the sialic acid type, such as an alpha2-6 linked SA versus an alpha2-3 linked SA, but the results here show that other factors can also significantly affect avidity.

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