Zika virus (ZIKV) infection of pregnant women can cause fetal microcephaly and other neurologic defects. We describe the development of a non-human primate model to better understand fetal pathogenesis. To reliably induce fetal infection at defined times, four pregnant rhesus macaques are inoculated intravenously and intraamniotically with ZIKV at gestational day (GD) 41, 50, 64, or 90, corresponding to first and second trimester of gestation. The GD41-inoculated animal, experiencing fetal death 7 days later, has high virus levels in fetal and placental tissues, implicating ZIKV as cause of death. The other three fetuses are carried to near term and euthanized; while none display gross microcephaly, all show ZIKV RNA in many tissues, especially in the brain, which exhibits calcifications and reduced neural precursor cells. Given that this model consistently recapitulates neurologic defects of human congenital Zika syndrome, it is highly relevant to unravel determinants of fetal neuropathogenesis and to explore interventions.

中文翻译：

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孕妇恒河猴猕猴接种羊膜内寨卡病毒会产生胎儿神经系统疾病。

孕妇的寨卡病毒（ZIKV）感染可引起胎儿小头畸形和其他神经系统缺陷。我们描述了一种非人类灵长类动物模型的发展，以更好地了解胎儿的发病机理。为了在确定的时间可靠地诱发胎儿感染，在妊娠第41、50、64或90天，分别对应于妊娠的头三个月和孕中期，给ZIKV静脉内和羊膜内接种四只怀孕的恒河猴。接种GD41的动物在7天后发生胎儿死亡，在胎儿和胎盘组织中病毒水平高，这提示ZIKV是死亡原因。其他三个胎儿则被带到了近胎并被安乐死。尽管没有人表现出明显的小头畸形，但都在许多组织（尤其是大脑）中显示ZIKV RNA，该组织表现出钙化和减少的神经前体细胞。