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

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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.