This project involves the molecular cloning, characterization, and functional mapping of the regulatory elements and regulatory genes (e.g., tat) of human immunodeficiency virus -1 and -2 (HIV- 1 and HIV-2). We have recently shown that several isolates of HIV-2, as well as simian immunodeficiency virus (SIV), possess a function tat gene, irrespective of their pathogenic potential in the natural host. Possibly relevant to virus latency, HIV-1 and HIV-2 gene expression can be stimulated by immune activation and heterologous transactivators such as human T-lymphotropic virus- 1 (HTLV-I) and oncogenic DNA viruses. DNA sequencing and functional mapping of the long terminal repeats (LTR), 3'orf and tat genes have revealed that the regulatory elements and genes of HIV-2 are related to HIV-1 and that various isolates of HIV-2, as well as SIV are more related among themselves than to HIV-1.