GENETIC AND BIOLOGICAL VARIABLITITY IN MATERNAL-INFANT STRAINS OF HIV-1

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目和 研究者（PI）可能从另一个NIH来源获得主要资金， 因此可以在其他CRISP条目中表示。所列机构为 中心，不一定是研究者的机构。 艾滋病毒-1母婴传播的因素定义不清，但在制定预防产前感染的战略方面至关重要。 母体病毒何时以及如何传播是很难确定的参数，因为只有20%至30%的艾滋病毒1感染母亲所生的婴儿受到感染。 然而，一种方法涉及定义婴儿中病毒的基因型复杂性和亲细胞性。 例如，感染婴儿的病毒可能是嗜巨噬细胞的，反映了它们感染培养物中的CD 4 T淋巴细胞和单核细胞衍生的巨噬细胞（MDM）的能力。 嗜巨噬细胞病毒可能导致神经系统症状或肺部并发症，这些症状在HIV-1婴儿和儿童中比在HIV-1感染的成人中更常见。 初步研究表明，表达CD 14的外周血单核细胞在新生儿和婴儿中感染，与成人相反。 拟议研究的具体目标将涉及在新生儿CDD 14+单核细胞中检测到HIV-1序列的频率、其在婴儿和儿童中随时间的持续性以及从CD 14+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的方法来评估CD 14+单核细胞中的病毒，并绘制HIV-1基因中有助于这些细胞感染性的决定因素。 这些研究为HIV-1的遗传变异性提供了基础，这些变异性可能有助于这些细胞的感染性。 这些研究为HIV-1的遗传变异性与体内病毒表型的关系提供了基础，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.