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

by Murilo Sena Amaral, Ernesto Goulart, Luiz Carlos Caires-J únior, David Abraham Morales-Vicente, Alessandra Soares-Schanoski, Roselane Paiva Gomes, Giovanna Gonçalves de Oliveira Olberg, Renato Mancini Astray, Jorge E. Kalil, Mayana Zatz, Sergio Verjovski-Almeida Zika virus (ZIKV) causes congenital Zika syndrome (CZS), which is characterized by fetal demise, microcephaly and other abnormalities. ZIKV in the pregnant woman circulation must cross the placental barrier that includes fetal endothelial cells and trophoblasts, in order to reach the fetus. CZS oc curs in ~1–40% of cases of pregnant women infected by ZIKV, suggesting that mothers’ infection by ZIKV during pregnancy is not deterministic for CZS phenotype in the fetus. Therefore, other susceptibility factors might be involved, including the host genetic background. We have previously shown that in three pairs of dizygotic twins discordant for CZS, neural progenitor cells (NPCs) from the CZS-affected twins presented differentialin vitro ZIKV susceptibility compared with NPCs from the non-affected. Here, we analyzed human-induced-pluripotent-stem-cell-derived (hiPSC-derived) trophoblasts from these twins and compared by RNA-Seq the trophoblasts from CZS-affected and non-affected twins. Followingin vitro exposure to a Brazilian ZIKV strain (ZIKVBR), trophoblasts from CZS-affected twins were significantly more susceptible to ZIKVBR infection when compared with trophoblasts from the non-affected. Transcriptome prof...
Source: PLoS Neglected Tropical Diseases - Category: Tropical Medicine Authors: Source Type: research