Our group is principally concerned with the molecular biology of HIV pathogenesis, particularly the pathogenesis of pediatric HIV disease. The course of HIV disease in pediatric patients differs substantially from the course of disease in adults. We are therefore particularly interested in trying to understand the involvement of host cell factors in HIV replication and the effect of HIV infection on the host cell. Our underlying hypothesis holds that there is one set of cellular conditions that is ideal for normal cellular growth and replication, that another set of conditions is ideal for viral replication, and that viruses (particularly HIV) have evolved ways of altering their host cells to enhance viral replication. During the past year, we have used cDNA microarray technology to begin to compile a comprehensive catalog of the cellular genes with altered expression during HIV replication and to attribute the changes in cellular gene expression to particular stages of the viral replication cycle and individual viral gene products. In support of our hypothesis, several cellular genes that are differentially regulated in the presence of particular viral gene products have previously characterized relationships to HIV replication. We have also constructed small arrays containing the entire set of genes from several herpesviruses, including the Kaposi's sarcoma-associated herpesvirus HHV8, and are using these tools to obtain a comprehensive description of the viral transcription programs and the cellular responses to viral infection.In other studies, we have partially cloned and have begun to characterize a cellular factor that binds to a site in the HIV LTR which is not active in lymphocytic cells, but is active in certain differentiated cell types. The factor appears to have an interesting pattern of tissue expression and interesting activities in addition to its sequence-specific DNA binding activity. Further studies aimed at completing the cloning of the factor and understanding its additional activities are in progress. In our clinical work, we have shown that peripheral blood lymphocyte telomeres shorten more rapidly during the first years of life, suggesting that lymphocytes turnover more rapidly during infancy than later in life. This may provide an explanation for the higher HIV viral loads and more rapid disease progression observed in pediatric HIV patients. It is 100% AIDS research. (About 10% of the work is also related to cancer.)
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