VIRAL & IMMUNE ELEMENTS IN EARLY PEDIATRIC HIV INFECTION

艾滋病毒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， 其在保护胎儿/婴儿方面非常有效， 大多数案件。各种传输设置的结果（猿猴 模型，成人异性恋和同性恋，和垂直）支持一个共同的主题 - 病毒表型/基因型优先传播和/或扩增 通常是同质的，嗜单核细胞/巨噬细胞的，非合胞体的， 诱导，具有相对缓慢的生长特性。据推测 最初的感染和胎盘内的传播 并且胎儿/新生儿由滋养层托管和协调， 单核细胞/巨噬细胞，后期病毒进化和募集 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假设为 预测最终的临床过程。本提案力求 建立表型（细胞培养试验）、基因型（DNA 测序）和定量（基于PCR的测定）特性的mv在 队列感染的新生儿，并监测病毒的特点， 在生命的第一年进化。这将与以下方面协调： 对感染的早期非特异性免疫反应的评估- 干扰素α产生作为单核细胞/巨噬细胞的标志物， 树突状细胞活化和NK细胞活性。最后，体外 将利用粘膜模型来研究跨粘膜传播 变量，重点是上皮细胞和免疫源性细胞。 仔细分析现有的和未来的样本，从围产期艾滋病毒 预计传播队列将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。

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.