Spread of a DENV mutant with defective 2’-O-methylation of the viral RNA genome.

(A) Genomic structure of the DENV-faR 2’-O-methylation mutant containing the E217A substitution in the NS5 protein (for further details see legend to Fig 4A). (B) Spread of the DENV-faR mutant in A549 reporter cells and activation of the IFN response. A549-IFIT1deGFP cells were infected with the DENV-faR E217A mutant at a MOI of 0.1 TCID50/cell. At the time points specified in the top of each panel, cells were fixed and processed for measurement by flow cytometry. (C) Model dynamics versus experimental data from (B) (solid lines and squares, respectively); for comparison, the model dynamics and data for wildtype DENV are reproduced from Fig 6C (dashed lines and circles, respectively). IFN-λ was measured by ELISA. Non-infected cells served as control. (D) Best-fit values and confidence bounds for the model parameters that have been allowed to differ between wildtype DENV and the 2’-O-methylation mutant. The model predicts that the virus production rate and the delay of IFN secretion decrease in case of the mutant (red box), whereas the delay of virus production and IFN secretion rate remain unchanged.