SRA

Zika virus (ZIKV) infection of maternal and placental cells at the maternal-fetal interface is associated with a spectrum of adverse pregnancy outcomes including fetal demise and pregnancy loss. Trophoblast cell types that comprise the placenta include cytotrophoblasts, syncytiotrophoblasts (STs), and extravillous trophoblasts (EVTs). To determine which trophoblast cells are permissive to ZIKV and to understand how infection impacts cellular gene expression, we utilized a macaque in vitro trophoblast stem cell (TSC) model. TSCs were derived from primary cytotrophoblasts and represent a proliferative trophoblast that can be differentiated into STs and EVTs. TSCs and ST3Ds (STs grown in suspension) were highly permissive to infection with ZIKV strain DAK AR 41524, whereas EVTs maintained a level of resistance to productive infection. The impact of ZIKV on cellular gene expression was determined by transcriptomic and miRNAome analysis. Infection of TSCs and ST3Ds results in increased expression of immune related genes, including those in the type I and type III interferon response. ZIKV exposure impacts EV protein, mRNA, and miRNA cargo, regardless of productive infection. Altogether, these findings suggest TSCs and STs of the macaque are permissive to ZIKV infection and that EV analysis has the potential to identify ZIKV infection. These findings provide a foundation for further ZIKV study and allow for potential ZIKV infection biomarker identification in a highly translational model. Overall design: 4 biological replicates per cell type (3 cell types total) were sequenced. The 3 cell types include trophoblast stem cells (TSCs), syncytiotrophoblasts (ST3Ds), and extravillous trophoblasts (EVTs). Each biological replicate was exposed to ZIKV or left as uninfected controls, for a total of 24 samples.