LD13184
- A virus replication cycle is initiated by virus binding to receptors presented on the surface of a host cell. An in-depth understanding of the very first steps of virus binding to cell membranes is therefore crucial for the development of antiviral therapies, vaccines and high-performance diagnostics. Studies of the initial interaction between a virus and the host cell membrane were so far mainly focused on identifying the binding sites on the virus and / or the cell membrane, while significantly less is known about the kinetics of the interaction. With single virus sensitivity, we quantify in this work the energy barrier for the virus-membrane association. We were able to discriminate between two structurally very similar receptors, which interaction kinetics could not be distinguished using conventional methods. We also observed that the virus release kinetics appears logarithmic over a long time span. Such interaction behavior is rarely observed in natural sciences and was earlier not reported in the context of virus binding. In our study, this feature has been explained by multiple receptor-virus contact points and membrane deformation. Such situations may occur at receptor-enriched cell-membrane regions with positive curvature, allowing us to suggest that the logarithmic kinetics may take place in vivo.
Description of the illustration:
Illustration of how surface-bound virus-like particles were used to probe their interaction with cell-membrane receptors incorporated into fluorescent-labeled lipid vesicles. By probing the rate of binding and the time individual vesicles remain bound (the residence time), we could simultaneously investigate weak (few receptor contacts) and strong (multiple receptor contacts) interactions. The virus-like particle was from the norovirus genogroup II.4 Dijon strain, being the major causative agent of acute viral gastroenteritis worldwide causing yearly up to 200, 000 children deaths, and the receptors were glycosylated sphingolipids.
