The development of interventions to prevent congenital Zika syndrome (CZS) has been limited by the lack of an established nonhuman primate model. Here we show that infection of female rhesus monkeys early in pregnancy with Zika virus (ZIKV) recapitulates many features of CZS in humans. We infected 9 pregnant monkeys with ZIKV, 6 early in pregnancy (weeks 6-7 of gestation) and 3 later in pregnancy (weeks 12-14 of gestation), and compared findings with uninfected controls. 100% (6 of 6) of monkeys infected early in pregnancy exhibited prolonged maternal viremia and fetal neuropathology, including fetal loss, smaller brain size, and histopathologic brain lesions, including microcalcifications, hemorrhage, necrosis, vasculitis, gliosis, and apoptosis of neuroprogenitor cells. High-resolution MRI demonstrated concordant lesions indicative of deep gray matter injury. We also observed spinal, ocular, and neuromuscular pathology. Our data show that vascular compromise and neuroprogenitor cell dysfunction are hallmarks of CZS pathogenesis, suggesting novel strategies to prevent and to treat this disease.

中文翻译：

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寨卡病毒感染的雌性恒河猴的胎儿神经病理学。

由于缺乏已建立的非人类灵长类动物模型，预防先天性寨卡综合症（CZS）的干预措施的发展受到了限制。在这里，我们显示了在妊娠初期用Zika病毒（ZIKV）感染雌性恒河猴，概括了人类CZS的许多特征。我们用ZIKV感染了9只怀孕的猴子，在怀孕初期（妊娠的第6-7周）感染了6只猴子，在妊娠后期（妊娠的第12-14周）感染了3只，并将发现的结果与未感染的对照组进行了比较。怀孕早期感染的猴子中有100％（6/6）表现出延长的母体病毒血症和胎儿神经病理学，包括胎儿丢失，脑尺寸变小和组织病理学脑损伤，包括微钙化，出血，坏死，血管炎，神经胶质增生和神经祖细胞凋亡。高分辨率MRI显示出一致的病灶，表明有深部灰质损伤。我们还观察到了脊柱，眼和神经肌肉的病理。我们的数据表明，血管受损和神经祖细胞功能异常是CZS发病机制的标志，表明了预防和治疗该疾病的新策略。