Jump to main content
Jump to site search


Cholesterol enhances influenza binding avidity by controlling nanoscale receptor clustering

Author affiliations

Abstract

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 via molecular dynamics simulations, where we find that cholesterol promotes small-scale clusters of glycosphingolipid receptors. We propose a model whereby cholesterol orders the monomeric state of glycosphingolipid receptors, reducing the entropic penalty of receptor association and thus favoring multimeric complexes without phase separation. This model explains how cholesterol and other sterols control the spatial organization of membrane receptors for influenza and increase viral binding avidity. A natural consequence of this finding is that local cholesterol concentration in the plasma membrane of cells may alter the binding avidity of influenza virions. Furthermore, our results demonstrate a form of cholesterol-dependent membrane organization that does not involve lipid rafts, suggesting that cholesterol's effect on cell membrane heterogeneity is likely the interplay of several different factors.

Graphical abstract: Cholesterol enhances influenza binding avidity by controlling nanoscale receptor clustering

Back to tab navigation

Supplementary files

Publication details

The article was received on 25 Jul 2017, accepted on 23 Jan 2018 and first published on 24 Jan 2018


Article type: Edge Article
DOI: 10.1039/C7SC03236F
Citation: Chem. Sci., 2018, Advance Article
  • Open access: Creative Commons BY-NC license
  •   Request permissions

    Cholesterol enhances influenza binding avidity by controlling nanoscale receptor clustering

    I. N. Goronzy, R. J. Rawle, S. G. Boxer and P. M. Kasson, Chem. Sci., 2018, Advance Article , DOI: 10.1039/C7SC03236F

    This article is licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported Licence. Material from this article can be used in other publications provided that the correct acknowledgement is given with the reproduced material and it is not used for commercial purposes.

    Reproduced material should be attributed as follows:

    • For reproduction of material from NJC:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the Centre National de la Recherche Scientifique (CNRS) and the RSC.
    • For reproduction of material from PCCP:
      [Original citation] - Published by the PCCP Owner Societies.
    • For reproduction of material from PPS:
      [Original citation] - Published by The Royal Society of Chemistry (RSC) on behalf of the European Society for Photobiology, the European Photochemistry Association, and RSC.
    • For reproduction of material from all other RSC journals:
      [Original citation] - Published by The Royal Society of Chemistry.

    Information about reproducing material from RSC articles with different licences is available on our Permission Requests page.

Search articles by author

Spotlight

Advertisements