FIG 4.

Biallelic defects in ZNFX1 deregulate ISGs’ expression and protection against viral infections in response to treatment with nucleic acids. A and B, Flow cytometry analysis of monocytes from P2.1 and a healthy control (CTRL) pretreated for 12 hours with different concentrations of LyoVec-poly(I:C) and subsequently infected with VSV–green fluorescent protein (GFP) for 5 hours. Representative plots of a single experiment showing VSV-GFP signal versus area of side scattered signal (SSC-A) (A) and mean percentage of VSV-GFP-positive monocytes relative to the unstimulated condition (no LyoVec-poly(I:C)) for 4 repeats (B). Error bars refer to the SD (n = 4). P values were calculated by using 2-way ANOVA and the Sidak multiple comparisons test. C, Transcriptomic analysis results for selected ISGs involved in antiviral responses are summarized in a heat map showing the mean difference in fold induction of ISGs expression from resting conditions in dermal fibroblasts from 4 patients (P1.2, P2.1, P3.2, and P5.2) over that in dermal fibroblasts from 4 different age-matched, healthy controls. Three different stimulations were used: 18 hours of intracellular poly(I:C) (LyoVec Poly (I:C)), 6 hours of soluble poly(I:C) (Poly (I:C)), or 18 hours of transfected poly(dA:dT) (LyoVec Poly (dA:dT)). D-F, The same data were used to study the activity of canonic double-stranded nucleic acids sensing pathways according to the Kyoto Encyclopedia of Genes and Genomes. Colored highlights indicate the rate of fold induction of gene expression in patients over that in the controls: red highlights the indicated increase, blue highlights the indicated decrease, and white boxes indicate no difference. Results from stimulation with LyoVec-poly(I:C) is shown in (D), with soluble poly(I:C) in (E) and LyoVec-poly(dA:dT) in (F). CASP8, Caspase 8.