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 immunodeficiency virus type 1 (HIV-1) transactivates tumor necrosis factor alpha and beta (TNFα and TNFβ) gene expression in HIV-1-infected and in tat-transfected T- lymphocytic and monocytic cell lines. The product encoded by the first exon of the tat gene (amino acids 1 to 72) is sufficient for this transactivation. Here we show that (i) the NF-κB and Sp1 binding sites of the TNFβ promoter are required for Tat-mediated transactivation and (ii) a predicted stem-loop structure in the TNFβ mRNA leader region, which resembles the Tat-responsive element of the HIV-1 long terminal repeat (TAR) and which is therefore termed TAR-like, is essential for TNFβ transactivation by Tat. These data suggest that similar promoter regulatory elements are necessary for Tat-mediated transactivation of both TNFβ and HIV-1 gene expression. This represents the first demonstration of a cellular gene with a regulatory element downstream of the transcriptional initiation site that, like TAR, may function as an RNA element.