Trophoblasts from Zika syndrome affected-twins are more susceptible to ZIKV than from non-affected

What is it about?

The Zika virus (ZIKV) infection in adults is usually characterized by mild flu-like symptoms, with most cases remaining asymptomatic. However, in the last years, widespread ZIKV infection was shown for the first time to be associated with congenital Zika syndrome (CZS) and death of neonates. It is estimated that CZS occurs in ~1–40% of cases of pregnant women infected by ZIKV, which suggests that different susceptibility factors might be involved, including the host genetic background. Here, by analyzing trophoblast cells that recapitulate the placenta from three pairs of dizygotic twins discordant for CZS, we were able to show that trophoblasts from CZS-affected twins were significantly more susceptible to ZIKV infection when compared with trophoblasts from the non-affected twins. We also provide a detailed picture of genes differentially expressed by trophoblasts from the discordant twins after infection with ZIKV. These genes can be further investigated as possible therapeutic targets to avoid viral dissemination into developing fetus’ tissues. Our results suggest that CZS might be caused, among other factors, by a decreased ability of the placenta to trigger the immune response to ZIKV infection in CZS-affected neonates, concomitant with a previously known deregulation of neural development genes in ZIKV-infected neuro-progenitor cells of these CZS-affected babies.

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Photo by Suhyeon Choi on Unsplash

Photo by Suhyeon Choi on Unsplash

Why is it important?

Here, we found that ZIKV infection elicited different responses in trophoblasts from CZS-affected and non-affected twins, highlighting that genes involved with extracellular matrix organization as well as with immune response activation in the placental tissue may contribute to modulate ZIKV infection outcome. Overall, our results showed that trophoblasts from non-affected twins have the ability to more efficiently activate genes that are known to play important roles in cell adhesion and in triggering the immune response to ZIKV infection in the placenta, and this may contribute to predict protection from ZIKV dissemination into fetuses’ neural tissues.

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