Zika virus pathophysiology during pregnancy

总体-项目总结/摘要 随着寨卡病毒（ZIKV）在美洲的到来，出生缺陷的激增。随着ZIKV的传播 在没有预先存在免疫力的人群中爆炸性地发生，整整一代孕妇， 他们的孩子可能有患先天性寨卡综合症的风险。不幸的是，几乎没有人知道 影响怀孕期间胎儿风险的参数和流行病学研究， 一群怀孕的妇女需要数年时间 我们开发了第一个非人灵长类动物模型，用于研究妊娠期间ZIKV感染的影响。 南西.这些研究中最具挑衅性的初步发现是母体病毒血症持续数周 怀孕猕猴的病毒血症持续时间为7-10天，而非怀孕猕猴的病毒血症仅持续7-10天。 蛋糕。该项目的主要假设是， 妊娠可预测胎儿患先天性寨卡综合征的风险。一个必然的结果是， 病毒血症可用于评估辅助因子和干预措施的影响， 生殖器寨卡综合征我们将通过三个综合项目来探索这一假设： 项目1。定义妊娠期持续ZIKV病毒血症对新生儿结局的影响。我们将 评估长期病毒血症、垂直传播和新生儿损伤之间的关系。 项目2.评估感染或接种疫苗是否引起对登革热病毒的免疫力 使用许可的疫苗，增加了怀孕期间持续ZIKV病毒血症的可能性或持续时间。 项目3。评估ZIKV特异性抗体的被动施用是否可以防止获得 当治疗性施用时，ZIKV的治疗效果和/或降低ZIKV的严重性。 ZIKV对整个美洲的孕妇及其胎儿/新生儿都是危险的。这种风险 它将持续至少几年，即使它最终被自然免疫力和广泛传播所削弱， 预防针该方案项目将为孕妇及其健康提供重要的新工具， 医疗服务提供者评估并潜在降低先天性寨卡综合征的风险。

Overall - Project Summary/Abstract A surge in birth defects accompanied the arrival of Zika virus (ZIKV) in the Americas. As ZIKV spreads explosively in populations with no pre-existing immunity, an entire generation of pregnant women and their babies may be at risk for congenital Zika syndrome. Unfortunately, nearly nothing is known about the parameters impacting fetal risk during pregnancy—and epidemiological studies following large co- horts of pregnant women will take years. We developed the first nonhuman primate model for studying the impact of ZIKV infection during preg- nancy. The most provocative initial finding from these studies is that maternal viremia persists for weeks to months in pregnant macaques, in contrast to viremia that lasts only 7-10 days in non-pregnant ma- caques. The key hypothesis of this Program Project is that prolonged maternal viremia during pregnancy predicts fetal risk of congenital Zika syndrome. A corollary is that duration of sustained viremia can be used to assess the impact of co-factors and interventions that modulate the risk of con- genital Zika syndrome. We will explore this hypothesis through three integrated projects: Project 1. Define the impact of sustained ZIKV viremia in pregnancy on neonatal outcomes. We will assess the relationship among prolonged viremia, vertical transmission, and neonatal injury. Project 2. Assess whether pre-existing immunity to dengue virus, elicited by infection or vaccination with a licensed vaccine, increases the likelihood or duration of sustained ZIKV viremia in pregnancy. Project 3. Evaluate whether passive administration of ZIKV-specific antibodies can prevent acquisi- tion and/or reduce the severity of ZIKV when administered therapeutically. ZIKV is dangerous to pregnant women and their fetuses/neonates throughout the Americas. This risk will persist for at least several years, even if it is eventually curtailed by natural immunity and widespread vaccination. This Program Project will provide important new tools for pregnant women and their health- care providers to assess, and potentially reduce, the risk of congenital Zika syndrome.