MODEL DEVELOPMENT FOR B19 PARVOVIRUS FETAL INFECTION

一种新的猿细小病毒（SPV），与人类非常相似 B19细小病毒，无论是在病毒基因组和临床疾病 由自然感染引起的，已经被发现。 此外，委员会认为， 实验性感染的临床和病理特点 猴子的SPV感染与人类B19感染非常相似。 长期目标是建立一个猴胎儿感染模型 与人类B19，开发改进的治疗或预防措施， 对于胎儿水肿（B19感染的已知破坏性后果）， 并阐明B19感染对胎儿造成的风险。 的 该项目的具体目标是建立实验室技术 用于检测活动物或尸检时的SPV DNA或抗体 探讨SPV在胎儿感染中的发病机制。 实验室技术包括斑点杂交和聚合酶 用链式反应原位检测血清和组织中的SPV 应用杂交和免疫细胞化学技术对SPV在小鼠脾细胞中定位 特异性细胞，以及用于检测 抗体滴度。 猴胎儿将在不同时间感染SPV 在妊娠的第一个三月晚期或第二个三月早期的时间点。 将通过超声波监测胎儿，以评估生长和发育 以及腹水或水肿的存在。 新生儿和婴儿 将对子宫内感染的猴子进行评估， 既往或持续感染SPV。 完整尸检 将对任何死亡或水肿胎儿和组织进行 并对血清进行SPV DNA或抗体评价。 相关性将 在胎儿被感染的妊娠阶段之间进行 最终的结果是胎儿水肿， 感染致死或正常妊娠

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.