MODEL DEVELOPMENT FOR B19 PARVOVIRUS FETAL INFECTION

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A new simian parvovirus (SPV) that is remarkably similar to the human B19 parvovirus, both in terms of the virus genome and clinical disease resulting from natural infection, has been discovered. Furthermore, the clinical and pathological features of experimental infection of monkeys with SPV closely resemble those of B19 infection in humans. The long-term objectives are to develop a monkey model of fetal infection with human B19, to develop improved therapies or preventive measures for hydrops fetalis (a known devastating consequence of B19 infection), and to clarify the risks posed to the fetus by B19 infection. The specific aims of this project are to establish laboratory techniques for detection of SPV DNA or antibody in live animals or at necropsy and to characterize the pathogenesis of fetal infection with SPV. 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 enzyme-linked immunosorbent assay for detection of antibody titers. Monkey fetuses will be infected with SPV at various time points in the late first or early second trimester of gestation. Fetuses will be monitored by ultrasound to assess growth and development and for the presence of ascites or hydrops. Neonatal and infant monkeys, infected in utero, will be evaluated for evidence of previous or persistent infection with SPV. Complete necropsies will be carried out on any dead or hydropic fetuses, and tissues and sera evaluated for SPV DNA or antibodies. Correlations will be made between the stage of gestation when fetuses were infected and the ultimate outcome, in terms of hydrops fetalis, persistent infection, lethality or normal gestation.