Multiscale perspectives of virus entry via endocytosis

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.

Figure 1

Illustration of the steps of virus entry via clathrin-mediated endocytosis. (A) Virus approaches the cell surface. (B) Biochemical interactions between ligands and receptors attract virus to the cell surface. (C) Virus attaches to the cell surface and signals the cell. (D) A clathrin-coated pit is formed around the bound virus. (E) A clathrin-coated vesicle is formed, and the dynamin at the neck region facilitate vesicle scission. (F) The vesicle travels to cell interior.

Figure 2

Electron microscopic analysis of HSV-1 uptake into cells. HSV-1 was bound to Vero (A), CHO-nectin-1 (B to D), or HeLa (E and F) cells for 2 h at 4°C. This was followed by a shift to 37°C for 20 min, and then the cells were processed for electron microscopy. Reproduced with permission from reference [29].

Figure 3

Imaging of HIV-1 in contact with T cells. (A-D) Four slices at different depths in a tomogram of the contact between HIV and T cells. (E) 3-D tomographically derived architecture of the contact region. Scale bar in (A) is 100 nm. Reproduced with permission from reference [53].

Figure 4

The interactions between gp120-coated cantilevers and cell receptors are specific. Reproduced with permission from reference [69].

Figure 5

Schematic of the mesoscale model for virus endocytic entry. The virus is modeled as a sphere decorated with ligands. The cell surface is modeled as a plasma membrane with diffusive receptors. The membrane surface is discretized by a curvilinear triangulate system.