VIRAL & IMMUNE ELEMENTS IN EARLY PEDIATRIC HIV INFECTION

病毒性的

• 批准号: 2887113
• 负责人: Paul E. Palumbo
• 金额: $ 23.31万
• 依托单位: UNIV OF MED/DENT OF NJ-NJ MEDICAL SCHOOL
• 依托单位国家: 美国
• 财政年份: 1995
• 资助国家: 美国
• 起止时间: 1995-09-30 至 2001-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2887113
• 关键词: dendritic cells; disease /disorder model; early diagnosis; genotype; helper T lymphocyte; human immunodeficiency virus; human subject; immunity; immunocytochemistry; interferon gamma; leukocyte activation /transformation; macrophage; monocyte; mucosa; natural killer cells; newborn human (0-6 weeks); nucleic acid sequence; pediatric AIDS; perinatal; phenotype; polymerase chain reaction; provirus; tissue /cell culture; vertical transmission; virus replication

The vertical transmission of HIV from mother to infant requires passage through the placenta or the newborn skin/mucous membrane surface, both of which are remarkably effective in protecting the fetus/infant in the majority of cases. Results from a variety of transmission settings (simian model, adult hetero- and homo-sexual, and vertical) support a common theme -the viral phenotype/genotype preferentially transmitted and/or amplified is generally homogenous, monocyte/macrophage-tropic, non-syncytium- inducing, with relatively slow growth characteristics. It is hypothesized that initial infection and dissemination events both within the placenta and the fetus/newborn are hosted and coordinated by trophoblasts and monocyte/macrophages with later viral evolution and recruitment of additional cell types. Early viral replication events and selection pressures together with the host immune response are hypothesized to be predictive of ultimate clinical course. This proposal endeavors to establish the phenotypic (cell culture assays), genotypic (DNA sequencing), and quantitative (PCR-based assays) properties of mv in a cohort of infected newborns and to monitor the characteristics of viral evolution through the first year of life. This will be coordinated with the evaluation of very early, non-specific immune response to infection - interferon alpha production as a marker of monocyte/macrophage and dendritic cell activation, and NK cell activity. Finally, an in vitro mucosal model will be utilized to study trans-mucosal transmission variables, focusing on both epithelial cells and cells of immune origin. Careful analysis of existing and future samples from a perinatal HIV transmission cohort is anticipated to provide insights into HIV transmission, prevention approaches, early viral pathogenesis and therapy.

艾滋病毒从母亲到婴儿的垂直传播需要通过 穿过胎盘或新生皮肤/粘膜表面 这对于保护胎儿/婴儿非常有效 大多数案件。来自各种传输设置的结果 模型，成人异性和同性恋以及垂直）支持一个共同的主题 - 优先传播和/或放大的病毒表型/基因型 通常是同质的，单核细胞/巨噬细胞的，非合成的 诱导，具有相对较慢的生长特征。它是假设的 最初的感染和传播事件都在胎盘中 胎儿/新生儿由滋养细胞托管和协调 单核细胞/巨噬细胞随后的病毒进化和募集 其他细胞类型。早期病毒复制事件和选择 压力与宿主免疫反应一起被认为是 预测最终临床过程。这项建议努力 建立表型（细胞培养分析），基因型（DNA） 测序）和MV在A中的定量（基于PCR的测定）特性 感染新生儿的队列并监测病毒的特征 在生命的第一年中演变。这将与 评估对感染的早期，非特异性免疫反应 - 干扰素α产生是单核细胞/巨噬细胞和 树突状细胞活化和NK细胞活性。最后，体外 粘膜模型将用于研究跨粘膜传播 变量，重点是上皮细胞和免疫起源细胞。 仔细分析来自围产期艾滋病毒的现有和未来样本 预计传播队列将为艾滋病毒提供见解 传播，预防方法，早期病毒发病机理和治疗。