Department of Viroscience, Erasmus Medical Center, Rotterdam, the Netherlands.
Department of Internal Medicine, Division of Pharmacology, Erasmus Medical Center, Rotterdam, the Netherlands.
PLoS Negl Trop Dis. 2022 Apr 20;16(4):e0010359. doi: 10.1371/journal.pntd.0010359. eCollection 2022 Apr.
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 placenta. Furthermore, results from studies in pregnant mice and non-human primates are conflicting 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.
孕妇感染 Zika 病毒（ZIKV）可导致小头畸形等严重出生缺陷。迄今为止，人们对于 ZIKV 如何穿过胎盘还不完全了解。此外，关于交叉反应性登革热病毒（DENV）抗体对胎盘 ZIKV 传播的作用，来自怀孕小鼠和非人类灵长类动物的研究结果存在矛盾。阐明 ZIKV 如何穿过胎盘以及哪些危险因素促成这种情况，对于风险评估和潜在的胎盘 ZIKV 传播干预策略非常重要。在这项研究中，我们使用离体人胎盘灌注模型来研究胎盘 ZIKV 传播以及交叉反应性 DENV 抗体对这种传播的影响。通过使用该模型，我们证明 DENV 抗体可显著增加灌注人胎盘对 ZIKV 的摄取，并且这种增加的摄取依赖于新生儿 Fc 受体。此外，我们表明交叉反应性 DENV 抗体可增强足月人胎盘外植体和原代胎儿巨噬细胞中的 ZIKV 感染，但不能增强原代滋养层细胞中的 ZIKV 感染。我们的数据支持这样一种假设，即交叉反应性 DENV 抗体的存在可能是胎盘 ZIKV 传播的一个重要危险因素。此外，我们证明离体胎盘灌注模型是一种相关的、对动物友好的模型，可用于研究胎盘病原体传播。
