To test if these substitutions are phenotypically relevant to the viral replication and/or modulation of IFN-signaling, the growth kinetics of the NS5 variants and the wildtype (WT) ZIKV-Natal were examined in WT-A549 cells (IFN-I response-competent), IFNAR−/− A549, and BVDV-Npro A549 cells (both are IFN-I response impaired; IFN-I denotes type I IFN) at a multiplicity of infection (MOI) of 0.1 over a 3-day period. This evidence concerns the gene IFNAR1 and infection.