VIRAL & IMMUNE ELEMENTS IN EARLY PEDIATRIC HIV INFECTION

病毒性的

• 批准号: 2076213
• 负责人: Paul E. Palumbo
• 金额: $ 20.05万
• 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 2000-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2076213
• 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.

HIV从母亲到婴儿的垂直传播需要通过 通过胎盘或新生儿皮肤/粘膜表面，两者 对保护胎儿/婴儿非常有效 大多数情况。各种传输设置的结果（猿 模型、成人异性恋和同性恋以及垂直）支持共同主题 -病毒表型/基因型优先传播和/或扩增 通常是同质的、单核细胞/巨噬细胞嗜性的、非合胞体的 具有诱导性，具有生长相对缓慢的特点。据推测 胎盘内的初始感染和传播事件 胎儿/新生儿由滋养层和协调 单核细胞/巨噬细胞随后进行病毒进化并招募 其他细胞类型。早期病毒复制事件和选择 假设压力与宿主免疫反应是 预测最终的临床过程。该提案力求 建立表型（细胞培养测定）、基因型（DNA mv 的测序）和定量（基于 PCR 的测定）特性 受感染新生儿队列并监测病毒特征 生命第一年的进化。这将与 对感染的非常早期的非特异性免疫反应的评估 - 干扰素α的产生作为单核细胞/巨噬细胞的标志物和 树突状细胞活化和 NK 细胞活性。最后，在体外 粘膜模型将用于研究跨粘膜传播 变量，重点关注上皮细胞和免疫起源细胞。 仔细分析现有和未来的围产期艾滋病病毒样本 传播队列有望提供对艾滋病毒的深入了解 传播、预防方法、早期病毒发病机制和治疗。