""""""""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. During the past year, we have shown that the expression of a splicing factor, SC35, increases during HIV infection. In order to understand further the involvement of host cell genes in HIV replication and the host response to infection we have begun to use newly available cDNA microarray to compile a catalog of cellular genes differentially expressed during HIV infection and to assign responsibility for any changes observed to particular stages of the viral life cycle and to particular viral gene products. We are also constructing 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 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 the kinetics of HIV replication in older children are similar to the kinetics in adults. Other clinical studies have shown that measurements of viral kinetics, CD4 cell number, and drug levels following the initiation of antiviral therapy can predict the clinical response to the antiviral therapy after several weeks, potentially enabling antiviral therapy to be optimized very rapidly. In another project, 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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