Zika virus (ZIKV) is a flavivirus with teratogenic effects on fetal brain, but the spectrum of ZIKV-induced brain injury is unknown, particularly when ultrasound imaging is normal. In a pregnant pigtail macaque (Macaca nemestrina) model of ZIKV infection, we demonstrate that ZIKV-induced injury to fetal brain is substantial, even in the absence of microcephaly, and may be challenging to detect in a clinical setting. A common and subtle injury pattern was identified, including (i) periventricular T2-hyperintense foci and loss of fetal noncortical brain volume, (ii) injury to the ependymal epithelium with underlying gliosis and (iii) loss of late fetal neuronal progenitor cells in the subventricular zone (temporal cortex) and subgranular zone (dentate gyrus, hippocampus) with dysmorphic granule neuron patterning. Attenuation of fetal neurogenic output demonstrates potentially considerable teratogenic effects of congenital ZIKV infection even without microcephaly. Our findings suggest that all children exposed to ZIKV in utero should receive long-term monitoring for neurocognitive deficits, regardless of head size at birth.

中文翻译：

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先天性寨卡病毒感染是一种无声病理，导致胎儿大脑神经源性输出丧失。

寨卡病毒 (ZIKV) 是一种黄病毒，对胎儿大脑具有致畸作用，但 ZIKV 引起的脑损伤范围尚不清楚，特别是在超声成像正常时。在 ZIKV 感染的怀孕猪尾猕猴 (Macaca nemestrina) 模型中，我们证明，即使没有小头畸形，ZIKV 引起的胎儿大脑损伤也很严重，并且在临床环境中可能难以检测。确定了一种常见且微妙的损伤模式，包括（i）室周 T2 高信号灶和胎儿非皮质脑容量的损失，（ii）室管膜上皮损伤并伴有潜在的神经胶质增生，以及（iii）晚期胎儿神经祖细胞的损失室下区（颞皮质）和颗粒下区（齿状回、海马）具有变形的颗粒神经元模式。胎儿神经源性输出的减弱表明，即使没有小头畸形，先天性寨卡病毒感染也可能产生相当大的致畸作用。我们的研究结果表明，所有在子宫内接触寨卡病毒的儿童都应该接受长期的神经认知缺陷监测，无论出生时头部大小如何。