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 4
Patterns (classes) of spatiotemporal infection dynamics.
First row: snapshots of spatial configurations of the epithelial cells. Color coded: uninfected (blue), infected (green), virus releasing (red), dead (black). TImes from left to right 4000 minutes (67 hours, 2 ¾ days), 8000 minutes (133 hours, 5 ½ days), 12000 minutes (200 hours, 8 ⅓ days), 16000 (267 hours, 11 days) and 20000 minutes (333 hours, 14 days). The right border of each snapshot aligns with the corresponding time in the time series. Second row: number of uninfected (orange), infected (green), virus-releasing (red) and dead (purple) epithelial cells vs time on a logarithmic scale (with 0 included for clarity). Third row: total extracellular cytokine (magenta) and total extracellular virus (brown) vs time on a logarithmic scale. Fourth row: value of the immune recruitment signal S (yellow) and number of immune cells (grey) vs time on a linear scale. (A) No immune response: infection propagates unopposed until all epithelial cells have died from intracellular virus. (B) Widespread infection: weak immune response slows propagation of the infection, but no uninfected cells survive at the end of the simulation. (C) Slowed infection: uninfected and infected epithelial cells coexist at the end of the simulation. (D) Containment of infection: no infected or virus-releasing epithelial cells remain, uninfected cells survive and virus remains in the extracellular environment at the end of the simulation. (E) Recurrence: the number of infected and virus releasing epithelial cells goes to zero, but persistent extracellular virus infects new epithelial cells later on. (F) Clearance: the number of infected and virus-releasing epithelial cells goes to zero and the level of extracellular virus is negligible at the end of the simulation. The model in (A) omits the immune response (components L1, I1-I4). All parameter values are as in Table 1 and Fig 3 except for kon and βdelay (S1 Table).