PATHOGENESIS AND THERAPY OF B19-INDUCED HYDROPS FETALIS

B19 引起的胎儿水肿的发病机制和治疗

• 批准号: 2889284
• 负责人: M. Gerard O'Sullivan
• 金额: $ 28.19万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-05-01 至 2000-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2889284
• 关键词: Macaca fascicularis; Parvoviridae; anemia; edema; embryo /fetus disorder; gestational age; pathologic process; pregnancy infection; virus diseases

Using a monkey model of human B19 parvovirus infection, the long term objectives are to clarify the pathogenesis of hydrops fetalis caused by B19 parvovirus, and to develop appropriate therapeutic regimens for this condition. Hydrops fetalis is a devastating and usually fatal consequence of fetal B19 parvovirus infection, the pathogenesis of which is poorly understood but that clinically may be amenable to therapy. Accordingly, the goal of this project is to better understand the pathogenesis of parvovirus fetal infection, using a unique simian parvovirus model of human B19 parvovirus infection. Our specific aims are to determine: (1) the natural history of fetal SPV infection, and (2) if hydrops fetalis is a consequence of SPV infection. Monkey fetuses will be inoculated with SPV on days 55 or 85 of gestation, i.e., before or after onset of immunocompetence (which occurs on gestation day 70), respectively. Fetuses will be monitored by ultrasound to assess growth and development and to detect hydrops fetalis (i.e., presence of ascites, pleural or pericardial effusions) if present. Blood samples will be obtained by ultrasound-guided cardiac puncture to monitor anemia, viremia and antibody response. Complete necropsies (including histopathology) will be carried out on fetuses recovered by cesarean section, dead or hydropic fetuses, and viable offspring. Tissues and sera will be evaluated for evidence of previous or persistent infection with SPV, including detection of virus and specific antibodies. Laboratory techniques include dot blot hybridization and polymerase chain reaction for detection of SPV in serum and tissues, in situ hybridization and immunocytochemistry for localization of SPV in specific cells, and Western blot assay for detection of antibody titers. Correlations between the time of fetal inoculation and the ultimate outcome (i.e., inapparent infection, anemia, transient or progressive hydrops fetalis, persistent infection and/or congenital anemia) will be examined. The natural history of any cases of hydrops fetalis arising from fetal SPV infection will be studied to determine the relationship to anemia and the outcome in terms of mortality or spontaneous resolution. The proposed studies will provide information on the pathogenesis of fetal parvovirus infection and hydrops fetalis that cannot be obtained in any other way because there is no other available appropriate animal model.

使用人B19细小病毒感染的猴模型， 目的是阐明胎儿水肿的发病机制， B19细小病毒，并为此制定适当的治疗方案 条件胎儿水肿是一种毁灭性的，通常是致命的后果 胎儿B19细小病毒感染，其发病机制不佳 但临床上可能适用于治疗。因此，委员会认为， 该项目的目标是更好地了解 细小病毒胎儿感染，使用独特的猴细小病毒模型， 人B19细小病毒感染。 我们的具体目标是确定：（1） 胎儿SPV感染的自然史，和（2）如果胎儿水肿 是SPV感染的结果。猴胎仔将接种 妊娠第55或85天SPV，即，发病前或发病后 免疫活性（发生在妊娠第70天）。 将通过超声波监测胎儿，以评估生长和发育 并检测胎儿水肿（即，存在腹水、胸膜或 心包积液）。 将通过以下方式采集血样： 超声引导心脏穿刺，以监测贫血、病毒血症和 抗体反应。完整尸检（包括组织病理学）将 对通过剖腹产术、死亡或水肿恢复的胎儿进行 胎儿和存活的后代。将对组织和血清进行评价， 既往或持续感染SPV的证据，包括 检测病毒和特异性抗体。 实验室技术 包括斑点印迹杂交和聚合酶链反应， 血清和组织中SPV的检测，原位杂交， 免疫细胞化学用于SPV在特定细胞中的定位，以及 用于检测抗体滴度的蛋白质印迹分析。之间的相关性 胎儿接种的时间和最终结果（即，隐性 感染、贫血、一过性或进行性胎儿水肿、持续性 感染和/或先天性贫血）进行检查。自然历史 任何由胎儿SPV感染引起的胎儿水肿病例， 研究以确定与贫血的关系以及 死亡率或自发性消退。拟议的研究将提供 关于胎儿细小病毒感染和水肿发病机制的信息 胎儿不能以任何其他方式获得，因为没有 其他合适的动物模型。