Transplacental Zika virus transmission in ex vivo perfused human placentas

Thomas Langerak; Michelle Broekhuizen; Peter Paul Alexander Unger; Lunbo Tan; Marion Koopmans; Eric van Gorp; A. H. Jan Danser; Barry Rockx

doi:10.1371/journal.pntd.0010359

Transplacental Zika virus transmission in ex vivo perfused human placentas

Thomas Langerak, Michelle Broekhuizen, Peter Paul Alexander Unger, Lunbo Tan, Marion Koopmans, Eric van Gorp, A. H. Jan Danser, Barry Rockx^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

A Zika virus (ZIKV) infection during pregnancy can result in severe birth defects such as microcephaly. To date, it is incompletely understood how ZIKV can cross the human pla-centa. Furthermore, results from studies in pregnant mice and non-human primates are con-flicting regarding the role of cross-reactive dengue virus (DENV) antibodies on transplacental ZIKV transmission. Elucidating how ZIKV can cross the placenta and which risk factors contribute to this is important for risk assessment and for potential intervention strategies for transplacental ZIKV transmission. In this study we use an ex vivo human placental perfusion model to study transplacental ZIKV transmission and the effect that cross-reactive DENV antibodies have on this transmission. By using this model, we demonstrate that DENV antibodies significantly increase ZIKV uptake in perfused human placentas and that this increased uptake is neonatal Fc-receptor-dependent. Furthermore, we show that cross-reactive DENV antibodies enhance ZIKV infection in term human placental explants and in primary fetal macrophages but not in primary trophoblasts. Our data supports the hypothesis that presence of cross-reactive DENV antibodies could be an important risk factor for transplacental ZIKV transmission. Furthermore, we demonstrate that the ex vivo placental perfusion model is a relevant and animal friendly model to study transplacental pathogen transmission.

Original language	English
Article number	e0010359
Journal	PLoS Neglected Tropical Diseases
Volume	16
Issue number	4
DOIs	https://doi.org/10.1371/journal.pntd.0010359
Publication status	Published - 20 Apr 2022

Bibliographical note

Funding Information:
This work was supported in part by the European Union?s Horizon 2020 Research and Innovation Programme under ZIKAlliance Grant Agreement no. 734548. This grant was received by EvG, MK and BR. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We would like to thank the study participants for donating their placenta for this study. Furthermore, we would like to thank Peter van de Run for assistance with tissue preparation for immunohistochemistry and Rugina Neuman and Zhongli Chen for assistance with patient recruitment and ex vivo placental perfusions.

Publisher Copyright:
© 2022 Langerak et al.

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Transplacental Zika virus transmission in exFinal published version, 3.65 MBLicence: CC BY

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title = "Transplacental Zika virus transmission in ex vivo perfused human placentas",

abstract = "A Zika virus (ZIKV) infection during pregnancy can result in severe birth defects such as microcephaly. To date, it is incompletely understood how ZIKV can cross the human pla-centa. Furthermore, results from studies in pregnant mice and non-human primates are con-flicting regarding the role of cross-reactive dengue virus (DENV) antibodies on transplacental ZIKV transmission. Elucidating how ZIKV can cross the placenta and which risk factors contribute to this is important for risk assessment and for potential intervention strategies for transplacental ZIKV transmission. In this study we use an ex vivo human placental perfusion model to study transplacental ZIKV transmission and the effect that cross-reactive DENV antibodies have on this transmission. By using this model, we demonstrate that DENV antibodies significantly increase ZIKV uptake in perfused human placentas and that this increased uptake is neonatal Fc-receptor-dependent. Furthermore, we show that cross-reactive DENV antibodies enhance ZIKV infection in term human placental explants and in primary fetal macrophages but not in primary trophoblasts. Our data supports the hypothesis that presence of cross-reactive DENV antibodies could be an important risk factor for transplacental ZIKV transmission. Furthermore, we demonstrate that the ex vivo placental perfusion model is a relevant and animal friendly model to study transplacental pathogen transmission.",

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AU - Rockx, Barry

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Transplacental Zika virus transmission in ex vivo perfused human placentas

Abstract

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