Cholesterol enhances influenza binding avidity by controlling nanoscale receptor clustering.

Goronzy IN, Rawle RJ, Boxer SG, Kasson PM

Chem Sci 9 (8) 2340-2347 [2018-02-28; online 2018-01-24]

Influenza virus infects cells by binding to sialylated glycans on the cell surface. While the chemical structure of these glycans determines hemagglutinin-glycan binding affinity, bimolecular affinities are weak, so binding is avidity-dominated and driven by multivalent interactions. Here, we show that membrane spatial organization can control viral binding. Using single-virus fluorescence microscopy, we demonstrate that the sterol composition of the target membrane enhances viral binding avidity in a dose-dependent manner. Binding shows a cooperative dependence on concentration of receptors for influenza virus, as would be expected for a multivalent interaction. Surprisingly, the ability of sterols to promote viral binding is independent of their ability to support liquid-liquid phase separation in model systems. We develop a molecular explanation for this observation

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PubMed 29520318

DOI 10.1039/c7sc03236f

Crossref 10.1039/c7sc03236f

mid NIHMS945310

pmc PMC5839467