Figure 1. Intrauterine (IU) inoculation of ZIKV during pregnancy results in productive infection and altered fetal outcomes.

(a) At embryonic day (E) 10, pregnant CD-1 mice underwent a mini-laparotomy in the lower abdomen for inoculation of either 10⁶ TCID₅₀ units of ZIKV (1968 Nigeria) or mock infection (IP, n=3 dams; IU, n=4 dams) by intraperitoneal (IP, n=8 dams) or intrauterine (IU, n=10 dams) routes. (b) At 48 h post-inoculation (hpi; E12), dams were killed, and fetal viability was determined as the percentage of fetuses within the inoculated uterine horn for ZIKV- and mock-infected dams that were viable. (c) ZIKV RNA, determined by qRT-PCR, was quantified from maternal serum, spleen, uterine horns, placenta and fetal brain tissues collected 48 hpi, with viral RNA in the placenta correlating with viral RNA in fetal tissues collected from IU ZIKV-inoculated dams (d). Infectious virus, determined by 50% tissue culture infectious dose (TCID50) (e), was quantified from maternal spleen, uterine horns, placenta and fetal brain tissues collected 48 hpi and correlated with viral RNA in fetal heads (f). For c,e, the median is indicated by the solid line for each tissue and the limits of detection (LOD) are indicated with dashed lines. Chi square test (b), two-way ANOVA with Bonferroni post-hoc correction (c,e), and Spearman correlation analysis (d,f), *=significant difference at P<0.05 within a route of inoculation, †=significant difference at P<0.05 between routes of inoculation.