GENETIC AND BIOLOGICAL VARIABILITY IN MATERNAL-INFANT STRAINS OF HIV-I

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。参与HIV-1母体传播的因素定义不清，但在设计预防产前感染的策略方面具有至关重要的意义。母体病毒何时以及如何传播是难以确定的参数，因为感染艾滋病毒的母亲所生的婴儿中只有20%至30%被感染。然而，一种方法涉及确定婴儿病毒的基因型复杂性和细胞性。例如，感染婴儿的病毒可能是嗜巨噬细胞的，这反映了它们在培养物中感染CD4 T淋巴细胞和单核细胞源性巨噬细胞（MDM）的能力。嗜巨噬细胞病毒可能是HIV-1婴儿和儿童比HIV-1感染成人更常见的神经系统症状或肺部并发症的原因。初步研究表明，与成人相比，表达CD14的外周单核细胞在新生儿和婴儿中受到感染。拟议研究的具体目标将解决HIV-1序列在新生儿CD14+单核细胞中检测到的频率，它们在婴儿和儿童中的持久性，以及从CD14+外周血单核细胞中分离出的病毒的特征。拟议的研究涉及许多新方法来评估CD14+单核细胞中的病毒，并绘制有助于这些细胞感染性的HIV-1基因中的决定因素。这些研究为HIV-1的相关遗传变异提供了基础，这可能有助于这些细胞的传染性。这些研究为HIV-1的遗传变异与体内病毒表型之间的关系提供了基础，并对开发预防HIV-1产前传播的疫苗策略具有重要意义。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Factors involved in maternal transmission of HIV-1 are poorly defined yet have critical importance in designing strategies to prevent prenatal infection. When and how maternal viruses are transmitted are difficult parameters to define because only 20 to 30% of infants born to HIV-1 infected mothers become infected. However, one approach involves defining the genotypic complexity and cytotropic properties of viruses in the infants. For example, viruses that infect infants may be macrophage tropic reflecting their ability to infect both CD4 T lymphocytes and monocyte-derived macrophages (MDM) in culture. Macrophage tropic viruses may account for the neurological symptoms or pulmonary complications that are more frequent among HIV-1 infants and children than among HIV-1 infected adults. Preliminary studies indicate that peripheral monocytes expressing CD14 are infected in neonates and infants, in contrast to adults. Specific aims of the proposed studies will address the frequency with which HIV-1 sequences are detected in neonatal CDD14 + monocytes, their persistence over time in infants and children, and the characteristics of the viruses isolated from CD14+ peripheral blood monocytes. The proposed studies involve a number of novel approaches to assess the virus in CD14+ monocytes and to map the determinants in HIV-1 genes that contribute to the infectivity of these cells. The studies provide the basis for relating genetic variability of HIV-1 that can contribute to the infectivity of these cells. The studies provide the basis for relating genetic variability of HIV-1 to phenotype of the virus in vivo and have significant implications for developing vaccine strategies to prevent prenatal transmission of HIV-1.