PATHOGENESIS AND THERAPY OF B19-INDUCED HYDROPS FETALIS

点击翻译按钮获取中文摘要

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.