VIRAL & IMMUNE ELEMENTS IN EARLY PEDIATRIC HIV INFECTION

艾滋病毒从母亲向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 它们在保护胎儿/婴儿方面非常有效 大多数情况下。各种变速箱设置(SIMAN)的结果 模特、成人异性恋者和同性恋者以及垂直人)支持一个共同的主题 -优先传播和/或扩增的病毒表型/基因型 一般均质，单核/巨噬细胞嗜性，非合胞体- 诱导性，具有生长相对缓慢的特点。这是假设的 最初的感染和传播都发生在胎盘内 而胎儿/新生儿由滋养层细胞和 单核/巨噬细胞与病毒的晚期进化和募集 其他单元格类型。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 最终临床病程的预测。这项建议致力于 建立表型(细胞培养分析)、基因分型(DNA 测序)和定量(基于聚合酶链式反应的分析)的特性。 新生儿感染队列和监测病毒特征 通过生命的第一年的进化。这将与 对感染的早期非特异性免疫反应的评估- 干扰素α的产生作为单核/巨噬细胞和 树突状细胞活化，NK细胞活性。最后，体外试验 粘膜模型将被用来研究跨粘膜传播 变量，侧重于上皮细胞和免疫来源的细胞。 仔细分析现有的和未来的围产期艾滋病毒样本 传播队列有望提供对艾滋病毒的洞察 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.