Zika virus pathophysiology during pregnancy

妊娠期间寨卡病毒的病理生理学

• 批准号: 9752458
• 负责人: David H. O'Connor
• 金额: $ 203.08万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-08-01 至 2023-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9752458
• 关键词: Affect; Americas; Antibodies; Antibody-Dependent Enhancement; Auditory; Autopsy; Avidity; Behavior; Biological Assay; Blood; Brain; Caring; Cognitive; Coloboma; Communicable Diseases; Congenital Abnormality; Dangerousness; Defect; Dengue Virus; Detection; Development; Epidemiology; Equilibrium; Eye; Eye Injuries; Fetal Development; Fetus; First Pregnancy Trimester; Functional disorder; Generations; Globulins; Health; Health Personnel; Hearing; Histopathology; Human; Immunity; Individual; Infection; Injury; International; Intervention; Life; Macaca; Macaca mulatta; Measures; Medical Imaging; Modeling; Monoclonal Antibodies; Mothers; Musculoskeletal; Natural Immunity; Neonatal; Neurologic; Newborn Infant; Passive Immunity; Pathologist; Performance; Plasma; Population; Pregnancy; Pregnant Women; Research; Research Personnel; Retinal; Risk; Sensory; Severities; Specialist; Structural defect; Structure; Study models; Testing; Therapeutic; Therapeutic Intervention; Tissues; Vaccination; Vaccines; Vertical Disease Transmission; Viremia; Virus Diseases; Virus Replication; Vision; Woman; ZIKV infection; Zika Virus; brain abnormalities; congenital zika syndrome; cross reactivity; epidemiology study; experience; fetal; in utero; malformation; neonatal injury; neonatal outcome; neonate; nonhuman primate; novel therapeutics; pregnant; prevent; programs; tool; transmission process; viral RNA; viral detection; viral transmission; virology

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.

总体-项目摘要/摘要 随着寨卡病毒(ZIKV)在美洲的到来，出生缺陷激增。随着ZIKV的传播 在没有预先存在免疫力的人群中爆炸性地，整整一代孕妇和 他们的婴儿可能有患先天性寨卡病毒综合症的风险。不幸的是，人们对此几乎一无所知 影响妊娠期间胎儿风险的参数--以及大规模联合妊娠后的流行病学研究 大量怀孕的妇女将需要数年的时间。 我们建立了第一个非人类灵长类动物模型，用于研究ZIKV感染对妊娠-产程的影响。 南希。这些研究的最具挑衅性的初步发现是，母亲的病毒血症会持续数周。 与非怀孕猕猴仅持续7-10天的病毒血症相比，怀孕猕猴的病毒血症可持续数月。 小酒馆。这一项目的关键假设是，长期的母体病毒血症 怀孕预示着胎儿患先天性寨卡病毒综合征的风险。推论是持续的持续时间 病毒血症可以用来评估调节感染风险的辅助因素和干预措施的影响。 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.确定妊娠期间持续的ZIKV病毒血症对新生儿结局的影响。我们会 评估延长的病毒血症、垂直传播和新生儿损伤之间的关系。 项目2.评估先前存在的对感染或接种疫苗引起的登革热病毒的免疫 有了许可的疫苗，增加了妊娠期间持续ZIKV病毒血症的可能性或持续时间。 项目3.评估被动注射ZIKV特异性抗体是否可以防止获得性- 治疗用药时，可减轻ZIKV的严重程度。 寨卡病毒对整个美洲的孕妇及其胎儿/新生儿都是危险的。这一风险 将持续至少几年，即使它最终被自然免疫力和广泛的 接种疫苗。该计划项目将为孕妇及其健康提供重要的新工具- 护理提供者评估并潜在地降低先天性寨卡病毒综合征的风险。