DETERMINANTS OF SIV AND HIV 1 TRANSPLACENTAL INFECTION

尽管有文献表明HIV-1能够感染发育中的胎儿 在某些情况下，关于病毒如何跨越子宫的大量数据 胎盘屏障缺失。一种动物模型将对 猪传染性支气管炎病毒和宿主感染因素的测定 发育中的胎儿。本提案中概述的工作重点是 假设使用HIV-1的猿猴SLVmac感染 胎儿与特定的病毒和宿主参数有关。 具体地说，为了检验这一假设并开发一个模型系统来 对发育中胎儿慢病毒感染的研究，我们计划：1) 确定生产性感染的必要条件 用Hofbauer和Hofbauer研究HIV-1和SLVmac的体外胎盘细胞 滋养层细胞培养和不同细胞的病毒表型 趋向性，2)研究外源性因素，如内毒素、阿片类药物或 特异性免疫调节细胞因子影响特异性艾滋病的生长 胎盘细胞培养中的病毒，3)决定病毒和临床 与感染猴的胎儿感染有关的参数 致病克隆的SLVmac病毒具有不同的细胞嗜性和 水坝临床参数及血吸虫感染状况研究 子代，以及4)确定病毒能够 通过对胎盘组织的详细研究跨越胎盘屏障 从胎儿和胎儿中获得的病毒分离株的特性 胎盘。

Despite documentation that HIV-1 is able to infect the developing fetus in utero in some cases, substantial data on how the virus is able to cross the placental barrier is lacking. An animal model would be useful for the determination of the viral and host factors involved in the infection of the developing fetus. The work outlined in this proposal focuses on the hypothesis that using the simian counterpart to HIV-1, SlVmac, infection of the fetus is associated with specific viral and host parameters. Specifically, to test this hypothesis and to develop a model system to study lentiviral infection of the developing fetus, we plan to: 1) determine the conditions necessary for the productive infection of placental cells in vitro with both HIV-1 and SlVmac, using both Hofbauer and trophoblast cell cultures and viral phenotypes with differing cellular tropisms, 2) study if exogenous factors, such as endotoxin, opiates, or specific immunoregulatory cytokines, influence growth of specific AIDS viruses in placental cell cultures, 3) determine the viral and clinical parameters associated with infection of the fetus by infecting monkeys with pathogenic cloned SlVmac viruses having varying cellular tropisms and studying the clinical parameters of the dams and infective status of the offspring, and 4) determine the mechanisms by which viruses are able to cross the placental barrier by a detailed study of placental tissue and characterization of the viral isolates obtained from the fetus and placenta.