A, Pedigree. B, Sanger sequencing confirmation of variant with IFNAR1 protein domains. C, IFNAR1 deficiency (immunoblot). D, Signaling by IFN-α2b or IFN-γ (1000 IU/mL, 30 m, immunoblot). E, ISG induction by IFN-α2b or IFN-γ (1000 IU/mL, 16 h, immunoblot). F, EMCV cytopathicity protection assay. G, ZIKV envelope (ENV), ISG15, RSAD2, and MX1 expression (immunoblot) in fibroblasts (H) ZIKV cytopathicity assay. Protection against ZIKV by IFN-α2b or IFN-γ (MOI 1.0, 1000 IU/mL, 24 h) by (I) immunoblot and (J) viability assay. Complementation with IFNAR1 but not empty vector (VEC) restores (K) ISG induction by IFN-α2b (1000 IU/mL, 16 h, immunoblot) and (L) IFN-α2b-mediated protection against EMCV. All experiments repeated n = 3 times in II:1 and control primary fibroblasts. Mean ± SD. ****P < .001, 2-way ANOVA with Tukey’s post-test. *nonspecific band. Abbreviations: ANOVA, analysis of variance; EMCV, encephalomyocarditis virus; IFN, interferon; IFNAR1, interferon alpha/beta receptor alpha chain; ISG, interferon-stimulated gene; MOI, multiplicity of infection; ZIKV, Zika virus.