MODEL DEVELOPMENT FOR B19 PARVOVIRUS FETAL INFECTION

一种与人类惊人相似的新猴细小病毒(SPV) B19细小病毒，从病毒基因组和临床疾病两方面来看 由自然感染引起的，已被发现。此外， 实验性肺炎的临床和病理特点 感染SPV的猴子与人类感染B19的猴子非常相似。 长期目标是开发一种猴子胎儿感染模型 人类B19，以开发改进的治疗或预防措施 对于胎儿积水(已知的B19感染的破坏性后果)， 并澄清B19感染对胎儿构成的风险。这个 该项目的具体目标是建立实验室技术 在活体动物体内或在身体剖检时检测SPV DNA或抗体 探讨胎儿SPV感染的发病机制。 实验室技术包括斑点杂交和聚合酶 链式反应原位检测血清和组织中的SPV SPV的杂交和免疫细胞化学定位研究 特异性细胞和酶联免疫吸附试验检测 抗体效价。猴胚胎会在不同的时间感染SPV 妊娠第一个月或第二个月早期的时间点。 胎儿将接受超声波监测，以评估生长发育情况。 以及腹水或积液的存在。新生儿和婴儿 在子宫内感染的猴子将被评估是否有证据表明 既往或持续感染SPV。完全性尸检 将在任何死亡或积水的胎儿和组织上进行 并对血清进行SPV DNA或抗体检测。关联性将 在胎儿被感染的妊娠期之间 从胎儿积水的角度来看，最终的结果是持续的 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.