DEVELOPMENT REGULATION OF HIV GENE EXPRESSION & LATENCY

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A key difference between congential and adult AIDS is the reduced or absent latency period observed in the congenital disease. Congenital AIDS has reduced or absent latency compared to adult AIDS. As newborn immune responses and lymphocytes differ qualitatively from adult's, this proposal's hypothesis is that newborn lymphocytes contain factors that alter HIV gene expression so that latency can not occur. In an analogous fashion, superinfection with DNA virus or immune stimulation are thought to end latency in adults. Planned studies will compare adult and cord blood lymphocyte-mediated HIV transcription, DNA binding proteins, and identify HIV sequences that interact with cord blood nuclear factors. The goal is to isolate and clone cord blood factors implicated in altered HIV expression and compare them with other factors thought to affect HIV expression. This may provide insight into latency and suggest new therapies. Preliminary results show substantial differences between cord and adult nuclear extract bonding to LTR fragments with regulatory sequences.