Differential gene expression elicited by ZIKV infection in trophoblasts from discordant congenital Zika syndrome twins

Zika virus (ZIKV) causes congenital Zika syndrome (CZS), which is characterized by fetal demise, microcephaly and other abnormalities such as learning, behavioral and muscle disabilities. CZS occurs in only ~1-40% of cases of pregnant women infected by ZIKV, suggesting that other susceptibility factors might be involved, including the host genetic background. Discordant twins represent a good case–control sample to test for the genetic contribution determining the fetuses' outcome of gestational infection with ZIKV. Here, sought to investigate the possible influence of host genetic background on CZS outcome, especially the role of placentas from dizygotic twins discordant for CZS. We analyzed hiPSC-derived trophoblasts from dizygotic twins discordant for CZS and compared by RNA-Seq the trophoblasts from CZS-affected and non-affected twins. hiPSC-derived trophoblasts recapitulates the primitive placenta formed during implantation. Confirming the influence of the host genome in CZS predisposition may open a path for drug development targeting specific pathways and for prediction of protection from ZIKV dissemination into fetuses' tis