FIG 5.

Maternal IFN-λ signaling induces fetal pathology. (A) Mating and infection timeline. Wild-type, Ifnar1^−/−, and Ifnar1^−/− Ifnlr1^−/− DKO mice were crossed to create pregnancies with differing IFN-λ responsiveness in maternal and fetal tissues, within dams lacking IFN-αβ signaling. Pregnant dams were infected at E7 with 1,000 FFU of ZIKV FSS13025 by subcutaneous inoculation in the footpad. Data are combined from 5 to 7 dams per group. (B) Representative images of the fetuses/resorptions from each cross. (C) Intact fetuses (not resorbed) were weighed. Fetuses with weights below 1 standard deviation of uninfected pregnancies were classified as having IUGR. Groups were compared by ANOVA; italicized letters indicate groups that are significantly different from each other (P < 0.05). (D) The percent of resorptions and IUGR in each pregnancy group. (E) The percent of intact fetuses in individual litters. (F and G) ZIKV viral loads in fetal head and maternal spleen were measured by qRT-PCR. (H) The sex of resorptions and intact fetuses was determined by PCR. (I and J) Ten-week-old nonpregnant females were infected with 1,000 FFU of ZIKV FSS13025 by subcutaneous inoculation in the footpad. Viral loads in serum (2, 4, 6 dpi) and tissues (6 dpi) were determined by qRT-PCR.