Zika virus (ZIKV) infection was first associated with Central Nervous System (CNS) infections in Brazil in 2015, correlated with an increased number of newborns with microcephaly, which ended up characterizing the Congenital Zika Syndrome (CZS). Here, we investigated the impact of ZIKV infection on the functionality of iPSC-derived astrocytes. Besides, we extrapolated our findings to a Brazilian cohort of 136 CZS children and validated our results using a mouse model. Interestingly, ZIKV infection in neuroprogenitor cells compromises cell migration and causes apoptosis but does not interfere in astrocyte generation. Moreover, infected astrocytes lost their ability to uptake glutamate while expressing more glutamate transporters and secreted higher levels of IL-6. Besides, infected astrocytes secreted factors that impaired neuronal synaptogenesis. Since these biological endophenotypes were already related to Autism Spectrum Disorder (ASD), we extrapolated these results to a cohort of children, now 6–7 years old, and found seven children with ASD diagnosis (5.14 %). Additionally, mice infected by ZIKV revealed autistic-like behaviors, with a significant increase of IL-6 mRNA levels in the brain. Considering these evidence, we inferred that ZIKV infection during pregnancy might lead to synaptogenesis impairment and neuroinflammation, which could increase the risk for ASD.

中文翻译：

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寨卡病毒感染会损害突触发生，诱发神经炎症，并可能是自闭症谱系障碍结果的环境危险因素

寨卡病毒 (ZIKV) 感染于 2015 年在巴西首次与中枢神经系统 (CNS) 感染相关，与小头畸形新生儿数量增加相关，最终成为先天性寨卡综合症 (CZS) 的特征。在这里，我们研究了 ZIKV 感染对 iPSC 衍生的星形胶质细胞功能的影响。此外，我们将我们的研究结果外推到巴西 136 名 CZS 儿童队列中，并使用小鼠模型验证了我们的结果。有趣的是，神经祖细胞中的 ZIKV 感染会损害细胞迁移并导致细胞凋亡，但不会干扰星形胶质细胞的生成。此外，受感染的星形胶质细胞失去了摄取谷氨酸的能力，同时表达更多的谷氨酸转运蛋白并分泌更高水平的IL-6。此外，受感染的星形胶质细胞分泌损害神经元突触发生的因子。由于这些生物内表型已经与自闭症谱系障碍 (ASD) 相关，因此我们将这些结果外推到一组现在 6-7 岁的儿童中，发现 7 名儿童患有 ASD 诊断 (5.14%)。此外，感染 ZIKV 的小鼠表现出类似自闭症的行为，大脑中 IL-6 mRNA 水平显着增加。考虑到这些证据，我们推断怀孕期间感染 ZIKV 可能会导致突触发生损伤和神经炎症，从而增加患自闭症谱系障碍 (ASD) 的风险。