Zika virus (ZIKV) infection during pregnancy causes a wide spectrum of congenital abnormalities and postnatal developmental sequelae such as fetal loss, intrauterine growth restriction (IUGR), microcephaly, or motor and neurodevelopmental disorders. Here, we investigated whether a mouse pregnancy model recapitulated a wide range of symptoms after congenital ZIKV infection, and whether the embryonic age of congenital infection changed the fetal or postnatal outcomes. Infection with ZIKV strain PRVABC59 from embryonic day 6.5 (E6.5) to E8.5, corresponding to the mid-first trimester in humans, caused fetal death, fetal resorption, or severe IUGR, whereas infection from E9.5 to E14.5, corresponding to the late-first to second trimester in humans, caused stillbirth, neonatal death, microcephaly, and postnatal growth deficiency. Furthermore, 4-week-old offspring born to dams infected at E12.5 showed abnormalities in neuropsychiatric state, motor behavior, autonomic function, or reflex and sensory function. Thus, our model recapitulated the multiple symptoms seen in human cases, and the embryonic age of congenital infection was one of the determinant factors of offspring outcomes in mice. Furthermore, maternal neutralizing antibodies protected the offspring from neonatal death after congenital infection at E9.5, suggesting that neonatal death in our model could serve as criteria for screening of vaccine candidates.

中文翻译：

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先天性寨卡病毒感染的胚胎阶段决定了小鼠的胎儿和产后结果

怀孕期间感染寨卡病毒 (ZIKV) 会导致广泛的先天性异常和产后发育后遗症，例如胎儿丢失、宫内生长受限 (IUGR)、小头畸形或运动和神经发育障碍。在这里，我们调查了小鼠妊娠模型是否重现了先天性 ZIKV 感染后的广泛症状，以及先天性感染的胚胎年龄是否改变了胎儿或产后结果。从胚胎第 6.5 天 (E6.5) 到 E8.5 感染 ZIKV 菌株 PRVABC59，对应于人类妊娠中期中期，导致胎儿死亡、胎儿再吸收或严重的 IUGR，而从 E9.5 到 E14.5 的感染，对应于人类孕早期到孕中期，导致死产、新生儿死亡、小头畸形和出生后生长不足。此外，在 E12.5 感染的水坝所生的 4 周大的后代表现出神经精神状态、运动行为、自主神经功能或反射和感觉功能异常。因此，我们的模型概括了人类病例中出现的多种症状，而先天性感染的胚胎年龄是小鼠后代结局的决定因素之一。此外，母体中和抗体保护后代在 E9.5 先天性感染后免于新生儿死亡，这表明我们模型中的新生儿死亡可以作为筛选候选疫苗的标准。先天性感染的胚胎年龄是小鼠后代结局的决定因素之一。此外，母体中和抗体保护后代在 E9.5 先天性感染后免于新生儿死亡，这表明我们模型中的新生儿死亡可以作为筛选候选疫苗的标准。先天性感染的胚胎年龄是小鼠后代结局的决定因素之一。此外，母体中和抗体保护后代在 E9.5 先天性感染后免于新生儿死亡，这表明我们模型中的新生儿死亡可以作为筛选候选疫苗的标准。