THE HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 TAT PROTEIN TRANSACTIVATES TUMOR-NECROSIS-FACTOR BETA-GENE EXPRESSION THROUGH A TAR-LIKE STRUCTURE

We have previously shown that the Tat protein of human immunodeficienc y virus type 1 (HIV-1) transactivates tumor necrosis factor alpha and beta (TNF alpha and TNF beta) gene expression in HIV-1-infected and in tat-transfected T-lymphocytic and monocytic cell lines. The product e ncoded by the first exon of the tat gene (amino acids 1 to 72) is suff icient for this transactivation. Here we show that (i) the NF-kappa B and Sp1 binding sites of the TNF beta promoter are required for Tat-me diated transactivation and (ii) a predicted stem-loop structure in the TNF beta mRNA leader region, which resembles the Tat-responsive eleme nt of the HIV-1 long terminal repeat (TAR) and which is therefore term ed TAR-like, is essential for TNFP transactivation by Tat. These data suggest that similar promoter regulatory elements are necessary for Ta t-mediated transactivation of both TNF beta and HIV-1 gene expression. This represents the first demonstration of a cellular gene with a reg ulatory element downstream of the transcriptional initiation site that , like TAR, may function as an RNA element.