Novel Model for Vertical Zika Virus Transmission via Decidual Cell-mediated Infection of Anchoring Villi

Vertical transmission of Zika virus (ZIKV) causes severe fetal defects, but the exact pathogenic mechanism is unclear. We identified up to a 10480-fold higher expression of viral attachment factors AXL, GAS6 and PROS1 and 3880-fold increase in ZIKV infectiousness/propagation in decidual cells (DCs) versus trophoblasts. Moreover, levels of viral attachment factors and ZIKV are significantly increased while expression of innate immune response genes are significantly decreased in first trimester versus term DCs. ZIKV-infected DC supernatants increased cytotrophoblast infection up to 252-fold compared to directly infected cytotrophoblasts. Tizoxanide treatment efficiently inhibited ZIKV infection in both cell types. We conclude that decidual cells may act as reservoirs for trimester-dependent placental transmission of ZIKV, accounting for the higher ZIKV infection susceptibility and more severe fetal sequelae observed in early versus late pregnancy. Moreover, tizoxanide is a promising agent in preventing perinatal ZIKV transmission. Primary cultured decidualized term decidual cells (TDC), cytotrophoblasts (CTB) and syncytiotrophoblasts (STB) obtained from term placental samples were subjected to RNA extraction, quantification, and evaluation, followed by hybridization on Illumina BeadChip. Three biological replicates were used (N=9 total samples).