DETERMINANTS OF SIV AND HIV 1 TRANSPLACENTAL INFECTION

SIV 和 HIV 1 经胎盘感染的决定因素

• 批准号: 3147305
• 负责人: DOUGLAS J RINGLER
• 金额: $ 15.66万
• 依托单位: HARVARD MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1991
• 资助国家: 美国
• 起止时间: 1991-09-30 至 1994-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3147305
• 关键词: AIDS; Macaca mulatta; communicable disease transmission; congenital infection; cytokine; disease /disorder model; embryo /fetus; endotoxins; human immunodeficiency virus 1; placenta; simian AIDSs; simian immunodeficiency virus; tissue /cell culture; virus replication

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.

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，在子宫内，有关病毒如何穿越子宫的大量数据 胎盘屏障缺乏。 动物模型将有助于 确定与感染有关的病毒和宿主因素 发育中的胎儿。 本提案中概述的工作重点是 假设使用 HIV-1 的猿猴对应物 SlVmac 感染 胎儿与特定的病毒和宿主参数相关。 具体来说，为了检验这个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) 确定产生性感染所需的条件 使用 Hofbauer 在体外对 HIV-1 和 SlVmac 胎盘细胞进行检测 和滋养层细胞培养物以及具有不同细胞的病毒表型 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，影响特定艾滋病的生长 胎盘细胞培养物中的病毒，3) 确定病毒和临床 与通过感染猴子而感染胎儿相关的参数 具有不同细胞向性的致病性克隆 SlVmac 病毒 研究母猪的临床参数和母猪的感染状况 后代，4）确定病毒能够传播的机制 通过对胎盘组织的详细研究来跨越胎盘屏障 从胎儿获得的病毒分离株的特征 胎盘。