Abstract
Most viruses take advantage of endocytic pathways to gain entry into host cells and initiate infections. Understanding of virus entry via endocytosis is critically important for the design of antiviral strategies. Virus entry via endocytosis is a complex process involving hundreds of cellular proteins. The entire process is dictated by events occurring at multiple time and length scales. In this review, we discuss and evaluate the available means to investigate virus endocytic entry, from both experimental and theoretical/numerical modeling fronts, and highlight the importance of multiscale features. The complexity of the process requires investigations at a systems biology level, which involves the combination of different experimental approaches, the collaboration of experimentalists and theorists across different disciplines, and the development of novel multiscale models.
Highlights
Viruses are small but masterful infectious agents infecting all types of organisms from bacteria, plants and animals to humans
The plasma membrane of a host cell represents the first physical barrier that viruses must overcome to gain entry. Some enveloped viruses such as herpes simplex virus type 1 (HSV-1), Sendai virus and human immunodeficiency virus (HIV) are able to penetrate into cells by direct fusion with the plasma membrane
We review recent technical advances in viral endocytic entry with an emphasis on the multiscale features of the process, and the collaborative and complementary roles played by experimentation and theoretical/ numerical modeling
Summary
Viruses are small but masterful infectious agents infecting all types of organisms from bacteria, plants and animals to humans. Theoretical continuum models Theoretical models have been developed to provide fundamental insights into viral endocytic entry into host cells In such models, the total free energy functional of the system is formulated by considering both energetic and entropic contributions in endocytic events, such as receptor diffusions, ligand-receptor interactions and membrane deformations. Stochastic mesoscale models A number of stochastic mesoscale models have been developed to study virus binding to host cell surfaces In these models, the viral particles are treated as rigid spheres whose surfaces are decorated with ligand proteins. English and Hammer [84] implemented Brownian Adhesive Dynamics (BRAD) to simulate the receptormediated binding of viruses In their model, the parameters were chosen to mimic the interactions between HIV particles and host cell surfaces. Due to the computational cost, the sizes of the NPs (or vesicles) considered in these simulations are relatively small (~10 nm in diameter)
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