Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology
Zika virus infection in pregnant rhesus macaques causes placental dysfunction and immunopathology
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DOI：
10.1038/s41467-017-02499-9
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发表时间：
2018-01-17
影响因子：
16.6
通讯作者：
Streblow, Daniel N.
中科院分区：
文献类型：
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作者：
Hirsch, Alec J.;Roberts, Victoria H. J.;Streblow, Daniel N.
怀孕期间感染寨卡病毒会导致胎儿生长受限和胎儿中枢神经系统畸形的风险增加，这些后果通常被称为先天性寨卡综合征。在这里，我们感染怀孕的恒河猴，并研究持续寨卡病毒感染对子宫胎盘病理、血流和胎儿生长发育的影响。尽管胎儿生长看似正常，胎儿-胎盘-母体感染持续存在，但先进的无创体内成像研究显示，胎盘氧储备受到显著影响，同时胎盘绒毛的氧通透性显著降低。观察到胎盘内的异常氧运输似乎是子宫血管炎和胎盘绒毛损伤在寨卡病毒病例的后果。此外，我们证明了强大的母体-胎盘-胎儿炎症反应后，寨卡病毒感染。该动物模型揭示了寨卡病毒感染与子宫胎盘病理之间的潜在关系，这种关系似乎会影响发育过程中胎儿的氧气输送。
Zika virus (ZIKV) infection during pregnancy leads to an increased risk of fetal growth restriction and fetal central nervous system malformations, which are outcomes broadly referred to as the Congenital Zika Syndrome (CZS). Here we infect pregnant rhesus macaques and investigate the impact of persistent ZIKV infection on uteroplacental pathology, blood flow, and fetal growth and development. Despite seemingly normal fetal growth and persistent fetal-placenta-maternal infection, advanced non-invasive in vivo imaging studies reveal dramatic effects on placental oxygen reserve accompanied by significantly decreased oxygen permeability of the placental villi. The observation of abnormal oxygen transport within the placenta appears to be a consequence of uterine vasculitis and placental villous damage in ZIKV cases. In addition, we demonstrate a robust maternal-placental-fetal inflammatory response following ZIKV infection. This animal model reveals a potential relationship between ZIKV infection and uteroplacental pathology that appears to affect oxygen delivery to the fetus during development.