Figure 3. Mathematical model.
(A) Microregions are linked virally because cell-free HSV-2 can seed surrounding regions, and immunologically based on overlapping CD8+ T-cell densities between regions (not shown). (B) Schematic for HSV-2 infection within a single genital tract microenvironment. Equations capture seeding of epithelial cells by neuronal HSV-2, replication of HSV-2 within epithelial cells, viral spread to other epithelial cells, cytolytic CD8+ T-cell response to infected cells, transition of cell-associated HSV-2 to cell-free HSV-2 following lysis of infected cells, and elimination of free virus and infected cells.
Figure 3—figure supplement 1. Spatial mathematical model.
Viruses produced from neurons (green), cell-associated viruses from epidermal cells (yellow), and cell-free viruses (orange) that form after rupture of epidermal cells, are distinguished in the model. Neuron-derived viruses are released throughout the genital tract and are responsible for ulcer initiation within specific regions (grey hexagons). Cell-associated HSV particles contribute to ulcer expansion (white circle) within a region. Cell-free particles initiate secondary ulcers in adjacent regions (upper right) leading to concurrent ulcers where HSV production occurs. Cytolytic CD8+ T-cell (purple circles) response is localized within each region. Regions have a maximum diameter of 6.5 mm. However, distance between regions is considered in terms of immunologic co-dependence rather than a physical distance. Seven of 300 total model regions are illustrated.