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

HIV-1 母婴病毒株的遗传和生物变异性

• 批准号: 7605430
• 负责人: Maureen M Goodenow
• 金额: $ 0.12万
• 依托单位: UNIVERSITY OF FLORIDA
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-23 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7605430
• 关键词: Accounting; Address; Adult; Biological; CD14 gene; CD4 Positive T Lymphocytes; Cells; Child; Computer Retrieval of Information on Scientific Projects Database; Frequencies; Funding; Genes; Genetic; Grant; HIV-1; Infant; Infection; Institution; Lung; Maps; Mothers; Neonatal; Neurologic; Numbers; Peripheral; Phenotype; Property; Research; Research Personnel; Resources; Source; Symptoms; Time; United States National Institutes of Health; Vaccines; Virus; base; design; in vivo; macrophage; monocyte; neonate; novel strategies; peripheral blood; prenatal; prevent; transmission process; virus characteristic

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.

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目和 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 涉及 HIV-1 母体传播的因素尚不清楚，但对于设计预防产前感染的策略至关重要。 母体病毒传播的时间和方式是很难确定的参数，因为感染 HIV-1 的母亲所生的婴儿中只有 20% 至 30% 受到感染。 然而，一种方法涉及定义婴儿病毒的基因型复杂性和亲细胞特性。 例如，感染婴儿的病毒可能是巨噬细胞嗜性的，这反映了它们能够感染培养物中的 CD4 T 淋巴细胞和单核细胞来源的巨噬细胞 (MDM)。 嗜巨噬细胞病毒可能是 HIV-1 婴儿和儿童中比 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，新生儿和婴儿的外周单核细胞表达 CD14 受到感染。 拟议研究的具体目标将解决新生儿 CDD14 + 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 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 HIV-1 基因中影响这些细胞感染性的决定因素。 这些研究为研究 HIV-1 的遗传变异性提供了基础，而 HIV-1 的遗传变异性可能导致这些细胞的感染性。 这些研究为将 HIV-1 的遗传变异性与体内病毒表型联系起来提供了基础，并对制定预防 HIV-1 产前传播的疫苗策略具有重要意义。