Vaccine and Infectious Disease Organization-International Vaccine Centre (VIDO-InterVac), University of Saskatchewan, Saskatoon, SK, Canada.
Methods Mol Biol. 2020;2142:181-195. doi: 10.1007/978-1-0716-0581-3_15.
Pigs are highly relevant to model human in utero Zika virus (ZIKV) infection because both species have similar physiology, genetics, immunity, fetal brain development, and postnatal brain growth. The virus causes persistent in utero infection and replicates in the fetal brain, fetal membranes, and placenta. Subclinical persistent in utero infection in mid-gestation also increases interferon alpha (IFN-α) levels in fetal blood plasma and amniotic fluid. Moreover, we demonstrated altered IFN-α responses in porcine offspring affected with subclinical in utero ZIKV infection. Elevated levels of in utero type I interferons were suggested to play a role in fetal pathology. Thus, the porcine model may provide an understanding of ZIKV-induced immunopathology in fetuses and sequelae in offspring, which is important for the development of targeted interventions. Here, we describe surgery, ultrasound-guided in utero injection, postoperative monitoring, sampling, and cytokine testing protocols.
猪在模型中与人的宫内寨卡病毒(ZIKV)感染高度相关,因为这两个物种具有相似的生理学、遗传学、免疫学、胎儿大脑发育和出生后大脑生长。该病毒导致持续性宫内感染,并在胎儿大脑、胎膜和胎盘内复制。妊娠中期亚临床持续性宫内感染也会增加胎儿血浆和羊水干扰素 α(IFN-α)水平。此外,我们还证明了受亚临床宫内 ZIKV 感染影响的猪后代的 IFN-α 反应发生改变。宫内Ⅰ型干扰素水平升高被认为在胎儿病理中起作用。因此,猪模型可能有助于了解寨卡病毒感染胎儿引起的免疫病理学和后代的后遗症,这对于开发靶向干预措施很重要。在这里,我们描述了手术、超声引导下宫内注射、术后监测、采样和细胞因子检测方案。