Detachment of Membrane Bound Virions by Competitive Ligand Binding Induced Receptor Depletion

Multivalent receptor-mediated interactions between virions and a lipid membrane can be weakened using competitive nonpathogenic ligand binding. In particular, the subsequent binding of such ligands can induce detachment of bound virions, a phenomenon of crucial relevance for the development of new antiviral drugs. Focusing on the simian virus 40 (SV40) and recombinant cholera toxin B subunit (rCTB), and using (monosialotetrahexosyl)ganglioside (GM1) as their common receptor in a supported lipid bilayer (SLB), we present the first detailed investigation of this phenomenon by employing the quartz crystal microbalance with dissipation (QCM-D) and total internal reflection fluorescence (TIRF) microscopy assisted 2D single particle tracking (SPT) techniques. Analysis of the QCM-D-measured release kinetics made it possible to determine the binding strength of a single SV40–GM1 pair. The release dynamics of SV40, monitored by SPT, revealed that a notable fraction of SV40 becomes mobile just before the release, allowing to estimate the distribution of SV40-bound GM1 receptors just prior to release.

Publication year: 2017
Authors: Parveen N. 1, Block S. 1, Zhdanov V.P. 1,2, Rydell G.E. 3, Höök F. 1
Affiliations:
1 – Department of Physics, Chalmers University of Technology, Gothenburg, Sweden
2 – Boreskov Institute of Catalysis, Russian Academy of Sciences, Novosibirsk, Russia
3 – Department of Infectious Diseases, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden
Published in: Langmuir, 2017, Vol. 33 (16), p. 4049–4056
DOI: 10.1021/acs.langmuir.6b04582

MP-SPR KEYWORDS

antiviral drug development GM1 receptor in a supported lipid bilayers (SLB) recombinant cholera toxin B subunit (rCTB) simian virus 40 (SV40) surface coverage virus-receptor interaction on lipid environment
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