Lack of 2’-O-methylation of the DENV RNA genome causes attenuation of virus spread by IFN action on infected cells.

(A) Schematic of the extended mathematical model. The inhibition of virus replication by early IFN signals is described explicitly. For further details see legend to Fig 6A. (B) Extent of predicted viral spread simulated by the model as a function of the delay from infection to IFN secretion and the virus production rate by infected cells that have not been inhibited by early IFN signals. The color code gives the relative difference from the spread of wildtype DENV in the full model at 96 h p.i. (C, D) Sensitivity analysis of the model parameters for infection with (C) wildtype DENV and (D) the E217A mutant. The response coefficients Ri of model parameter i were calculated with the full model. Shown are virus-related (blue bars) and IFN-specific (green bars) parameter effects on infected cells.