We have begun to catalogue the differences in gene expression between human immunodeficiency virus (HIV)-infected cells (ACH-2) and uninfected cells (A3.01) to dissect, at the molecular level, the mechanism of HIV- induced immune dysregulation. Using mRNA differential display, we have identified 40 to 50 gene fragments whose regulation in CD4+ T cells appears to be modulated by infection with HIV. Several classes of expression were noted: genes expressed only in infected or uninfected cells, genes up- or down-regulated upon treatment with tumor necrosis factor-alpha (TNF-alpha) and, within this latter group, genes whose TNF- alpha stimulation is infection modulated. We have used similar technology to identify six genes whose expression in primary CD8+ T cells is altered during progression from clinical latency to acquired immunodeficiency syndrome. Ongoing work is aimed at verification/ analysis of apparently affected genes to ascertain their role in HIV pathogenesis/immune dysregulation. In addition, we hope to continue to exploit these technologies to better understand the effects of HIV on various cell types, including primary T cells (CD4+ and CD8+) and acutely-infected cells.