Life cycle synchronization is a viral drug resistance mechanism
Fig 1
Schematic of model for viral dynamics in a patient undergoing antiviral treatment.
(A) Diagram of basic viral dynamics model incorporating the infected cell maturation process. The population of cells is comprised of healthy cells x, one or more stages of immature infected cells w, and mature (virus-producing) infected cells y. The maturation time is the time it takes for an infected cell to pass through all the maturation phases. (B) Probability distribution functions of maturation times, when the maturation process happens as a series of n consecutive steps. The maturation times are gamma-distributed with the same average of 2 days, for different numbers of maturation steps (n = 1, 2, 10, 25). (C) The viral infectivity β(t) relative to the viral infectivity in the absence of the drug β0 fluctuates in response to drug levels (blue line). In the simple on-off model (a step function), drug levels are “on” for a fraction f of the time between doses (red shading), reducing viral fitness to zero, and “off” for the rest of the interval (viral fitness returns to baseline). (D) Time course of infection levels when the maturation time is fixed to τ = 2 days (yellow line) and τ = 3 days (blue line), and the drug dosage is modeled as a periodic step function. The synchronized strain (maturation time of 2 days, yellow line) reaches higher time-averaged infection level than the unsynchronized strain. In these examples, we use drug period T = 2 days and drug efficacy f = 0.85.