Stochastic vs. deterministic modeling of intracellular viral kinetics.
Within its host cell, a complex coupling of transcription, translation, genome replication, assembly, and virus release processes determines the growth rate of a virus. Mathematical models that account for these processes can provide insights into the understanding as to how the overall growth cycle depends on its constituent reactions. Deterministic models based on ordinary differential equations can capture essential relationships among virus constituents. However, an infection may be initiated by a single virus particle that delivers its genome, a single molecule of DNA or RNA, to its host cell. Under such conditions, a stochastic model that allows for inherent fluctuations in the levels of viral constituents may yield qualitatively different behavior. To compare modeling approaches, we developed a simple model of the intracellular kinetics of a generic virus, which could be implemented deterministically or stochastically. The model accounted for reactions that synthesized and depleted viral nucleic acids and structural proteins. Linear stability analysis of the deterministic model showed the existence of two nodes, one stable and one unstable. Individual stochastic simulation runs could access and remain at the unstable node. In addition, deterministic and averaged stochastic simulations yielded different transient kinetics and different steady-state levels of viral components, particularly for low multiplicities of infection (MOI), where few virus particles initiate the infection. Furthermore, a bimodal population distribution of viral components was observed for low MOI stochastic simulations. The existence of a low-level infected subpopulation of cells, which could act as a viral reservoir, suggested a potential mechanism of viral persistence.
Srivastava, R; You, L; Summers, J; Yin, J
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