Abstract
The objective of this critical review is to provide an overview of how emerging bioanalytical techniques are expanding our understanding of the complex physicochemical nature of virus interactions with host cell surfaces. Herein, selected model viruses representing both non-enveloped (simian virus 40 and human norovirus) and enveloped (influenza A virus, human herpes simplex virus, and human immunodeficiency virus type 1) viruses are highlighted. The technologies covered utilize a wide range of cell membrane mimics, from supported lipid bilayers (SLBs) containing a single purified host membrane component to SLBs derived from the plasma membrane of a target cell, which can be compared with live-cell experiments to better understand the role of individual interaction pairs in virus attachment and entry. These platforms are used to quantify binding strengths, residence times, diffusion characteristics, and binding kinetics down to the single virus particle and single receptor, and even to provide assessments of multivalent interactions. The technologies covered herein are surface plasmon resonance (SPR), quartz crystal microbalance with dissipation (QCM-D), dynamic force spectroscopy (DFS), total internal reflection fluorescence (TIRF) microscopy combined with equilibrium fluctuation analysis (EFA) and single particle tracking (SPT), and finally confocal microscopy using multi-labeling techniques to visualize entry of individual virus particles in live cells. Considering the growing scientific and societal needs for untangling, and interfering with, the complex mechanisms of virus binding and entry, we hope that this review will stimulate the community to implement these emerging tools and strategies in conjunction with more traditional methods. The gained knowledge will not only contribute to a better understanding of the virus biology, but may also facilitate the design of effective inhibitors to block virus entry.
Highlights
While attachment factors are only involved in the attachment of the virus particles to the cell surface, cellular receptors promote the entry of the virus
The analysis suggested that the Simian virus 40 (SV40) virus needs to bind at least 4 GM1 lipid molecules to achieve firm/irreversible attachment to the supported lipid bilayers (SLBs), thereby providing a molecular picture for the strong non-linearity observed in the SV40 surface coverage
Single particle tracking of GAG-bound Herpes simplex virus type 1 (HSV-1) particles using total internal reflection fluorescence (TIRF) microscopy revealed that GAG-bound viruses have the capability of diffusing laterally on predominantly immobile GAG chains (Fig. 5C), presumably through a hopping or rolling behavior resulting from a molecular exchange mechanism where the formation and dissolution of individual bonds between viral glycoproteins and neighboring cellular GAGs allow for a lateral motion [100]
Summary
Viruses are obligate intracellular parasites requiring access to the intracellular environment in order to replicate. Binding of the virus particle to the plasma membrane of the target cell is an important first step in the viral replication process It is mediated by specific receptors and attachment factors [1]. Due to the importance of virus-receptor interactions for viral entry, virologists, chemical biologists, biochemists, and biophysicists alike have all shown great interest in untangling the complex mechanisms governing receptor-mediated viral uptake Such knowledge does contribute to a better understanding of infection biology, but may facilitate the Physicochemical tools for studying virus interactions with targeted cell membranes in a molecular and. This review focuses on selected key biomolecular processes mediating virus attachment and entry, all relying on the dynamic molecular interactions between viral proteins and cell-surface molecules It highlights how recent methodological developments can contribute to a deeper understanding of such dynamic interactions. Influenza A virus is included in this review because of its well-characterized interaction with sialylated
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