MODEL DEVELOPMENT FOR B19 PARVOVIRUS FETAL INFECTION

B19 细小病毒胎儿感染的模型开发

• 批准号: 6031039
• 负责人: M. Gerard O'Sullivan
• 金额: $ 10.86万
• 依托单位: UNIVERSITY OF MINNESOTA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-06-01 至 2001-06-14
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6031039
• 关键词: Macaca fascicularis; Parvoviridae; amniocentesis; antiviral antibody; ascites; communicable disease diagnosis; disease /disorder model; embryo /fetus disorder; embryo /fetus monitoring; enzyme linked immunosorbent assay; gestational age; immunocytochemistry; in situ hybridization; infant animal; model design /development; newborn animals; polymerase chain reaction; serology /serodiagnosis; simian virus; virulence; virus DNA; virus diseases; western blottings

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.

一种与人类极其相似的新猿猴细小病毒（SPV） B19细小病毒，无论是病毒基因组还是临床疾病 已被发现是由自然感染引起的。 此外， 实验性感染的临床和病理特征 感染 SPV 的猴子与人类感染 B19 病毒的猴子非常相似。 长期目标是开发胎儿感染的猴模型 与人类 B19 一起开发改进的疗法或预防措施 对于胎儿水肿（B19 感染的已知破坏性后果）， 并澄清 B19 感染对胎儿造成的风险。 这 该项目的具体目标是建立实验室技术 用于检测活体动物或尸检中的 SPV DNA 或抗体 并确定胎儿感染 SPV 的发病机制。 实验室技术包括斑点杂交和聚合酶 用于原位检测血清和组织中 SPV 的链式反应 杂交和免疫细胞化学用于 SPV 定位 特定细胞和酶联免疫吸附测定法检测 抗体滴度。 猴胎儿在不同时期都会感染SPV 时间点在妊娠早期或中期。 将通过超声波监测胎儿以评估生长和发育 以及是否存在腹水或积水。 新生儿和婴儿 将评估在子宫内感染的猴子的证据 既往或持续感染 SPV。 完整尸检 将对任何死亡或水肿的胎儿和组织进行 并评估血清中的 SPV DNA 或抗体。 相关性将 在胎儿被感染的妊娠阶段之间进行 以及最终的结果，就胎儿水肿而言，持续存在 感染、致死或正常妊娠。