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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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.


Overall, development of congenital Zika syndrome might result, among other factors, from a concomitant decreased ability of the placenta to respond to ZIKV infection in the CZS-affected neonates, along with a deregulation of neural development genes in ZIKV-infected Neural Progenitor Cells of these CZS-affected neonates. Moreover, further understanding of the participation of immune mediators identified here, such as the chemokines RANTES/CCL5 and IP10, in the trophoblast response to ZIKV infection may open a path for drug development or repurposing to possibly inhibit viral replication or avoid viral dissemination into fetus’ tissues.

Sergio Verjovski-Almeida
Universidade de Sao Paulo Campus da Capital

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This page is a summary of: Differential gene expression elicited by ZIKV infection in trophoblasts from congenital Zika syndrome discordant twins, PLoS Neglected Tropical Diseases, August 2020, PLOS,
DOI: 10.1371/journal.pntd.0008424.
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