A modular framework for multiscale, multicellular, spatiotemporal modeling of acute primary viral infection and immune response in epithelial tissues and its application to drug therapy timing and effectiveness
Fig 3
Simulation of the progression of infection in a patch of epithelial tissue of size 360 μm x 360 μm starting from a single infected cell for a representative simulation using the baseline parameters given in Table 1.
(A) Snapshots of spatial configuration vs time, showing progression of a simulated infection. Columns, left to right: 0 minutes (time of initial infection), 4000 minutes (67 hours, 2 ¾ days) after infection, 8000 minutes (133 hours, 5 ½ days), 12000 minutes (200 hours, 8 ⅓ days), 16000 minutes (267 hours, 11 days), and 20000 (333 hours, 14 days) minutes. First row: epithelial-cell layer composed of uninfected (blue), infected (green), virus-releasing (red) and dead epithelial cells (black). Second row: position of immune cells in the extracellular environment layer. Third row: concentration of extracellular virus field. Fourth row: concentration of extracellular cytokine field. Fifth row: concentration of extracellular oxidative agent field. Fields are shaded on a logarithmic scale: red corresponds to the chosen maximum value specified in the first panel and blue corresponds to six orders of magnitude lower than the maximum value; colors saturate for values outside this range. (B-D) Simulation time series. (B) Number of uninfected (orange), infected (green), virus-releasing (red) and dead (purple) epithelial cells vs time on a logarithmic scale (0 values are overlaid at a non-logarithmic tick for clarity). (C) Total extracellular cytokine (magenta) and total extracellular virus (brown) vs time on a logarithmic scale. (D) Value of the immune recruitment signal S (yellow) and number of immune cells (grey) vs time on a linear scale. Simulations use periodic boundary conditions in the plane of the epithelial sheet, and Neumann conditions [57] normal to the epithelial sheet.