New technology permits new experimental designs. The development of large-scale genomic assays has made it possible to monitor simultaneously and on an unprecedented scale the expression of genes in a cell following a perturbation. The sheer magnitude of genes analyzed provides useful profiles of genes expressed and signal transduction pathways activated yielding insights into cellular processes, many of which would not have been considered a priori. This type of discovery-driven research contrasts with the more traditional hypothesis-driven approach found in biological research. The two approaches are, however, complementary. Both approaches are included in this proposal, in that very distinct phenotypes will be compared. First, virus contacting quiescent versus activated cells and second, viral tropism for CXCR-4 and CCR-5 co-receptors. There may be an interrelationship between these phenotypes as well. Specifically, we will investigate the modulation of cellular gene expression by HIV-1 infection of CD4+ T cells with wild type and mutant HIV as well as with individually expressed HIV gene products. In addition, we will determine the modulation of cellular gene expression during the infection of CD4+ T lymphocytes in the context of a X4 or R5 tropism.
