Life cycle synchronization is a viral drug resistance mechanism
Fig 2
Equilibrium infection level for the single-strain deterministic model, as a function of the average maturation time.
Viral dynamics were simulated under periodic antiviral therapy given by the simple on-off model with a period (T) of 2 days and varying drug efficacy (f). The infection level (heat map color) is measured as the concentration of mature infected cells (y) once a steady-state has been reached. Each calculation included only a single virus strain with average maturation time 1/m (maturation rate of nm for each stage). (A) Results with n = 1 maturation steps. (B) Results with n = 10 maturation steps. (C) Results with n = 25 maturation steps. (D) Results with fixed maturation time τ = 1/m. The white dotted lines show where the average maturation time is equal to an integer multiple of the drug period. For all shown simulations, we assume the death rate of immature cells to be zero (dw = 0). Results shown for 41 different drug efficacies between f = 0.6 and f = 1.0, for 101 different strains with average maturation times between 1 and 6 days. A version of the results with more resolution around the threshold drug efficacy (f = 0.9) is in S2 Fig and a version with dw > 0 is in S3 Fig.