Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, SK S7N 5E3, Canada.
Department of Physiology, Department of Obstetrics and Gynaecology, University of Toronto, Toronto, ON M5S 1A8, Canada.
EBioMedicine. 2017 Nov;25:73-86. doi: 10.1016/j.ebiom.2017.09.021. Epub 2017 Sep 21.
Outcomes of Zika virus (ZIKV) infection in pregnant women vary from the birth of asymptomatic offspring to abnormal development and severe brain lesions in fetuses and infants. There are concerns that offspring affected in utero and born without apparent symptoms may develop mental illnesses. Therefore, animal models are important to test interventions against in utero infection and health sequelae in symptomatic and likely more widespread asymptomatic offspring. To partially reproduce in utero infection in humans, we directly inoculated selected porcine conceptuses with ZIKV. Inoculation resulted in rapid trans-fetal infections, persistent infection in conceptuses, molecular pathology in fetal brains, fetal antibody and type I interferon responses. Offspring infected in utero showed ZIKV in their fetal membranes collected after birth. Some in utero affected piglets were small, depressed, had undersized brains, and showed seizures. Some piglets showed potentially increased activity. Our data suggest that porcine model of persistent in utero ZIKV infection has a strong potential for translational research and can be used to test therapeutic interventions in vivo.
孕妇感染 Zika 病毒（ZIKV）的结果从无症状后代的出生到胎儿和婴儿的异常发育和严重脑损伤不等。人们担心受宫内感染影响且出生时无症状的后代可能会患上精神疾病。因此，动物模型对于测试针对宫内感染和有症状及可能更广泛无症状后代的健康后遗症的干预措施非常重要。为了部分重现人类宫内感染，我们直接用 ZIKV 接种了选定的猪胚胎。接种导致快速的跨胎感染、胚胎中的持续感染、胎儿大脑中的分子病理学、胎儿抗体和 I 型干扰素反应。宫内感染的后代在出生后收集的胎膜中显示出 ZIKV。一些宫内受影响的仔猪体型较小、情绪低落、大脑较小，并出现癫痫发作。一些仔猪表现出潜在的活动增加。我们的数据表明，持续宫内 ZIKV 感染的猪模型具有很强的转化研究潜力，可用于体内测试治疗干预措施。
