Figure 5. Role of the ZIKV NS5–hSTAT2 interaction in ZIKV NS5-mediated degradation of hSTAT2 and type I IFN signaling suppression.
a, Immunoblot analysis of 293T cells transfected with indicated plasmids encoding wild-type or mutant NS5-HAs at three different amounts using antibodies against HA, hSTAT2, and GAPDH. b, VSV-GFP infection of A549 cells treated with 1:2 serial dilutions of the supernatants derived from poly(I:C)-stimulated 293T cells, non-transfected (mock), or transfected with NS5 or NS5 MutYRDH. Representative images of three independent experiments. Scale bars, 20 μm. c, Immunoblot of NS5 and GAPDH (top) and qRT-PCR analysis of ISG54 and OAS-1 mRNAs (bottom) of non-transfected 293T cells (mock), or 293T cells transfected with plasmids encoding wide-type or mutant NS5-HAs, followed by treatment with IFN for 18 hr. Data in graphs are mean ± s.d. (n=3 independent transfections). Statistical analysis used two-tailed Student’s t-test; ns, p > 0.05. d, IFN-β promoter-driven luciferase activity assay. Fold increase of interferon β production activated by (left to right) RIG-2CARD, TBK-1 and IRF3 in 293T cells transfected with empty pCAGGS vector, GFP, WT or MutYRDH ZIKV NS5. Data are mean ± s.d. (n=3 independent transfections). Uncropped blots for a,b and source data for b,d are in Supplementary Data 1 and 2, respectively.