Department of Pathology, University of Miami Leonard M. Miller School of Medicine, 1951 NW 7th Ave Room 2340, Miami, FL, 33136, USA.
Department of Immunology and Microbiology, The Scripps Research Institute, 3215 Merryfield Row Immunology 308, San Diego, CA, 92121, USA.
Nat Commun. 2018 Apr 24;9(1):1624. doi: 10.1038/s41467-018-04056-4.
Zika virus (ZIKV) infection of pregnant women is associated with pathologic complications of fetal development. Here, we infect pregnant rhesus macaques (Macaca mulatta) with a minimally passaged ZIKV isolate from Rio de Janeiro, where a high rate of fetal development complications was observed. The infection of pregnant macaques with this virus results in maternal viremia, virus crossing into the amniotic fluid (AF), and in utero fetal deaths. We also treated three additional ZIKV-infected pregnant macaques with a cocktail of ZIKV-neutralizing human monoclonal antibodies (nmAbs) at peak viremia. While the nmAbs can be effective in clearing the virus from the maternal sera of treated monkeys, it is not sufficient to clear ZIKV from AF. Our report suggests that ZIKV from Brazil causes fetal demise in non-human primates (NHPs) without additional mutations or confounding co-factors. Treatment with a neutralizing anti-ZIKV nmAb cocktail is insufficient to fully stop vertical transmission.
寨卡病毒（ZIKV）感染孕妇与胎儿发育的病理并发症有关。在这里，我们用来自里约热内卢的一种低代次传播的寨卡病毒分离株感染怀孕的恒河猴（Macaca mulatta），在那里观察到胎儿发育并发症的发生率很高。这种病毒感染怀孕的猕猴会导致母体病毒血症、病毒进入羊水（AF）以及宫内胎儿死亡。我们还在另外三只感染寨卡病毒的怀孕猕猴的病毒血症高峰期用寨卡病毒中和人源单克隆抗体（nmAbs）鸡尾酒疗法进行治疗。虽然 nmAbs 可以有效地从治疗猴的血清中清除病毒，但不足以从 AF 中清除 ZIKV。我们的报告表明，来自巴西的寨卡病毒在没有其他突变或混杂的伴随因素的情况下导致非人类灵长类动物（NHP）的胎儿死亡。用中和抗寨卡病毒的 nmAb 鸡尾酒疗法治疗不足以完全阻止垂直传播。
