PATHOGENICITY OF HIV ISOLATES: ROLE IN FETAL TRANSMISSON

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These investigations seek to understand the role of variants of HIV present in infected, pregnant women and the immune responses to them in governing the transmission of HIV from mother to fetus. We postulate that transmission may occur when a critical immune response against a variant isolate does not occur or is lost. We will isolate biological clones of HIV from infected mothers and infants, and examine their growth rate and syncytia-forming capacity using, in part, a new assay that quantitates the ability of infected cells to kill noninfected CD4 positive cells by a syncytia type of interaction that does not require that a productive infection be established in the target cell. In addition we will study the role of CD8 cells from infected individuals to limit the outgrowth of different biological clones of HIV from a given patient, as an example of cellular immunity to autologous HIV, and as a potential method for selecting out biological variants. We will compare the binding to CD4 of gp120 from isolates of different syncytia-forming capacities, using both cell binding and an enzyme-linked assay we have developed. In order to learn more about CD4 immune responses to HIV antigens, we will study the proliferative responses of lymphocytes from infected mothers and infants to a panel of HIV recombinant proteins and synthetic peptides representing selected regions of gp120. The characteristics of the biological clones of HIV isolated from mothers and infants and the immune responses to them will be analyzed as to their association with the transmission of HIV from mother to fetus.