INTERACTION OF HIV WITH ISOLATED PLACENTAL CELLS

HIV 与分离的胎盘细胞的相互作用

• 批准号: 3147302
• 负责人: GORDON C DOUGLAS
• 金额: $ 17.37万
• 依托单位: UNIVERSITY OF CALIFORNIA AT DAVIS
• 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 1995-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3147302
• 关键词: 2'3' dideoxynucleoside; AIDS; CD4 molecule; HIV infections; acid base balance; antiviral antibody; cell adhesion; colony stimulating factor; communicable disease transmission; complement; congenital infection; fibroblasts; gestational age; human immunodeficiency virus; human tissue; immunocytochemistry; integrins; interleukin 1; interleukin 2; interleukin 6; lymphocyte; macrophage; monocyte; placenta; placental transfer; scanning electron microscopy; tissue /cell culture; tumor necrosis factor alpha; vascular endothelium; virus infection mechanism; zidovudine

Evidence for the transmission of HIV from mother to fetus via the placenta has been documented but the mechanism of transmission is unknown. The overall aim of this proposal is to determine the cellular and molecular mechanisms involved in the placental transport of HIV from maternal blood to the fetus. This objective will be pursued by taking advantage of our ability to obtain pure population of human trophoblast cells and our ability to demonstrate cell-mediated infection of these cells in vitro. Placental syncytiotrophoblast is in direct contact with maternal blood and virus must cross this epithelium before reaching stromal cells, endothelial cells and, eventually, the fetal bloodstream. The first specific aim will focus on characterizing the role of lymphocytic/monocytic cells in the cell-mediated infection of syncytiotrophoblast. We will use immunocytochemical and transmission and scanning electron microscopic techniques to study the kinetics of the cell-cell interaction and the infection process. The cellular pathway by which HIV enters the cells will be defined. The possibility that cytokines or other factors released by lymphocytic/monocytic cells play a role in the cell mediated infection process will be studied. Other experiments will establish the nature of the adhesion molecules involved in cell-cell binding and analyze the role of antibody and CD4 in the infection process. In the second specific we aim will attempt to determine whether the interaction of HIV with syncytiotrophoblast varies as a function of gestational age by characterizing the nature of HIV infection of cells obtained from first and second trimester placentas. In the third specific aim we will determine whether anti-viral dideoxynucleosides prevent HIV infection of placental cells and whether cell function is compromised. In the last specific aim we will focus on placental macrophages, fibroblasts and endothelial cells. As well as characterizing viral internalization and release we will examine in vitro infected cells for alterations in the secretion of cytokines and growth factors. Information gained should be useful in designing strategies to prevent HIV transmission.

通过艾滋病毒从母亲传播到胎儿的证据 已记录了胎盘，但传输的机理是 未知。 该提案的总体目的是确定细胞 以及参与HIV胎盘转运的分子机制 胎儿的孕产妇。该目标将通过采取 我们获得人类滋养细胞纯种群的能力的优势 细胞和我们证明细胞介导的感染的能力 细胞体外。 胎盘合成素细胞直接接触 孕产妇和病毒必须在到达之前越过这一上皮 基质细胞，内皮细胞，最终是胎儿血液。 第一个具体目标将重点是表征 细胞介导的感染中的淋巴细胞/单核细胞 合成细胞素细胞。 我们将使用免疫细胞化学和传播 和扫描电子显微镜技术来研究 细胞 - 细胞相互作用和感染过程。 细胞 将定义HIV进入细胞的途径。 可能性 淋巴细胞/单核细胞释放的细胞因子或其他因素 将研究在细胞介导的感染过程中发挥作用。 其他实验将建立粘附分子的性质 参与细胞细胞结合并分析抗体和CD4的作用 在感染过程中。 在第二个特定中，我们的目标将尝试 确定HIV与合成型肌细胞的相互作用是否有所不同 通过表征艾滋病毒的性质，作为胎龄的函数 从第一和第二孕期获得的细胞感染。 在第三个特定目的中，我们将确定是否抗病毒 二乙氧基核苷可防止胎盘细胞的HIV感染以及是否 细胞功能受到损害。 在最后一个特定目标中，我们将重点关注 胎盘巨噬细胞，成纤维细胞和内皮细胞。 也 表征病毒内在化和释放，我们将在 体外感染细胞，以改变细胞因子的分泌和 增长因素。 获得的信息应该在设计中很有用 防止艾滋病毒传播的策略。