DETERMINANTS OF SIV AND HIV 1 TRANSPLACENTAL INFECTION

尽管有文件表明，HIV-1能够感染发育中的胎儿， 在某些情况下，关于病毒如何能够穿过子宫的大量数据 缺乏胎盘屏障。 动物模型将有助于 确定参与感染的病毒和宿主因素， 发育中的胎儿 本提案中概述的工作重点是 假设使用HIV-1的猿类对应物SlVmac， 胎儿与特定的病毒和宿主参数有关。 具体来说，为了检验这一假设，并开发一个模型系统， 研究发育中胎儿的慢病毒感染，我们计划：1） 确定生产性感染的必要条件 胎盘细胞在体外与HIV-1和SlVmac，使用Hofbauer 和滋养层细胞培养物以及具有不同细胞分化的病毒表型 向性，2）研究是否有外源性因素，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AIDS生长 胎盘细胞培养物中的病毒，3）确定病毒和临床 与通过感染猴感染胎儿相关的参数 具有不同细胞向性的致病性克隆S1 Vmac病毒， 研究母鼠的临床参数和感染状况， 后代，以及4）确定病毒能够 通过对胎盘组织的详细研究， 从胎儿中获得的病毒分离株的表征， 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.