Quantitative model of DENV spread and IFN response.

(A) Schematic of the mathematical model: Virus replicates in infected cells after time delay τR and produces virus with time delay τV and rate vV, which can infect susceptible cells (blue arrow). Infected cells produce IFN after time delay τF with rate vF, which protects susceptible cells (solid green arrow) and can induce antiviral genes in infected cells (dashed green arrow). For further details of the mathematical model see S1 Supplementary Methods. (B) Spread of DENV-faR virus and activation of the IFN response. A549-IFIT1deGFP cells were infected with DENV-faR at a MOI of 0.1 TCID50/cell. At time points specified in the top of each panel, cells were fixed and processed for measurement by flow cytometry. (C) Best fit of the mathematical model to two independent experiments; the initial conditions for the number of susceptible cells are specific to each experiment whereas the model parameters are the same for both experiments. The numbers of susceptible, DENV-faR positive (i.e. infected) and IFIT1deGFP positive (i.e. protected) cells have been taken from the flow-cytometry data (the comparatively small number of double-positive cells was counted as infected); IFN-λ was measured in experiment 2 by ELISA. Non-infected cells served as control.