PATHOGENESIS AND THERAPY OF B19-INDUCED HYDROPS FETALIS

使用人类B19细小病毒感染的猴子模型，长期 目的是阐明由以下原因引起的胎儿积水的发病机制 B19细小病毒，并为此开发适当的治疗方案 条件。胎儿积水是一种毁灭性的后果，通常是致命的。 胎儿B19细小病毒感染，其发病机制较差 可以理解，但在临床上可能会接受治疗。因此， 这个项目的目标是更好地了解糖尿病的发病机制 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感染的自然病史，以及(2)胎儿是否积水 是SPV感染的结果。猴子胚胎将接种疫苗 妊娠55天或85天，即发病前后的SPV 免疫活性(发生在妊娠第70天)。 胎儿将接受超声波监测，以评估生长发育情况。 并检测胎儿积水(即是否存在腹水、胸膜或 如果有心包积液)。血液样本将通过以下方式获取 超声引导心脏穿刺术监测贫血、病毒血症和 抗体反应。完全尸检(包括组织病理学)将 对剖宫产发现的死胎或积水的胎儿进行手术 胎儿和可存活的后代。将对组织和血清进行评估 既往或持续感染SPV的证据，包括 病毒和特定抗体的检测。实验室技术 包括斑点杂交和聚合酶链式反应 血清和组织中SPV的检测，原位杂交和 免疫细胞化学用于SPV在特定细胞的定位，以及 免疫印迹法检测抗体效价。两者之间的相关性 胎儿接种的时间和最终结果(即看不见的 持续性感染、贫血、一过性或进行性胎儿积水 将检查感染和/或先天性贫血)。自然历史 任何由胎儿SPV感染引起的胎儿积水将是 研究以确定与贫血的关系和结果 死亡或自发消退。拟议的研究将提供 胎儿细小病毒感染和积水发病机制的研究进展 无法通过任何其他方式获得的胎儿，因为没有 其他可用的合适的动物模型。

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.