Figure 1. Mortality, viral burden, and size of mouse fetuses after maternal infection with ZIKV.

A. Schematic depiction of two models of infection during pregnancy. Model 1: WT males were crossed with Ifnar1^−/− dams. Pregnant dams were infected subcutaneously with ZIKV (10³ FFU) on E6.5 or E7.5 followed by harvest on E13.5, or 15.5, respectively. Model 2: WT males were crossed with WT dams. Pregnant dams treated with 1 mg of an anti-IFNAR antibody on days −1, +1, and +3 relative to ZIKV (10³ FFU) or DENV-3 (10³ FFU) infection. Mice were sacrificed on E13.5 or E15.5 and fetuses and placentas were harvested for measurements of fetal size by crown-rump length (CRL) and occipito-frontal (OF) diameter. B. E13.5 uteri from ZIKV-infected WT and Ifnar1^−/− dams. Most Ifnar1^+/− fetuses carried by Ifnar1^−/− dams died in utero and had undergone resorption, leaving only the residual placenta. In the lower three panels are representative images of fetuses carried by ZIKV-infected WT and mock-infected Ifnar1^−/− dams, the latter of which exhibited growth restriction at E15.5. C. Fetus survival on E13.5 after infection with ZIKV on E6.5. Mice were either treated with three 1 mg doses of control or anti-Ifnar antibody (left two bars) or untreated mock- or ZIKV-infected Ifnar1^−/− dams (right two bars). Data are representative of at least 3 independent experiments with 1 pregnant female dam per experiment. The n for each group is indicated above each bar. ****, P < 0.0001. D. Fetus size as assessed by CRL × OF diameter in E13.5 fetuses following E6.5 infection of the indicated pregnant dams with either ZIKV or DENV-3. Bars indicate the mean size of 8-20 fetuses from 2 or 3 independent experiments from fetuses carried by 2 to 3 pregnant dams. ***, P < 0.0005; ****, P < 0.0001. E and F. Viral burden was measured by qRT-PCR assay from the fetal head and placenta on E13.5 after infection at E6.5. Symbols represent individual fetuses pooled from several independent experiments with the exception of 4 intact Ifnar1^+/− fetal heads that were carried by a single dam. Bars indicate the mean of 4 to 17 mice per group. Dotted lines represent the limit of sensitivity of the assay. *, P < 0.05 **, P < 0.005; ***, P < 0.0005; ****, P < 0.0001. G. Fetus survival on E15.5 after infection with ZIKV on E7.5. Data are representative of at least 2 independent experiments with 1 pregnant female dam per experiment. The n for each group is indicated above each bar. ****, P < 0.0001. H. Fetus size as assessed by CRL × OF diameter in E15.5 fetuses following E7.5 infection of the indicated pregnant dams with ZIKV. ****, P < 0.0001. I-K. Viral burden was measured by qRT-PCR assay from maternal serum, spleen, and brain at E13.5. Symbols are derived from individual animals and pooled from 2 or 3 independent experiments. Bars indicate the mean of 4 to 5 mice per group. Dotted lines represent the limit of sensitivity of the assay. See also Figure S1.