Differential regulation of bcl-2 and c-fos genes by HIV-1 tat protein in serum-starved and activated lymphoid T cells

The regulatory Tat protein of HIV-1 exerts a pleyotropic activity on the survival and proliferation of different cell types both in vivo and in vitro. We investigated the effect of Tat protein on Bcl-2 and cfos gene expression and cell survival in Jurkat T cell line and primary peripheral blood mononuclear cells (PBMC). Jurkat cells stably expressing tat cDNA were cotransfected with a plasmid containing Bcl-2 promoter in front of the bacterial cloramphenicol acetyltransferase CAT (Bcl-2 Pr/CAT) or with a plasmid containing the c-fos promoter (FC3, from -711 to +42) in front of CAT. While Bcl-2/CAT was significantly activated in serum-starved Jurkat-/a; cells, c-fos/CAT required the addition of 15% PCS or 10'7M PMA plus 5 u.g/ml PHA in order to be activated by Tat. In further experiments, we found that Jurkat-/a/ showed a significant increase of endogenous Bcl-2 and c-fos mRNA and protein expression under serum-free and serum-containing cultures, respectively. The overexpression of Bcl-2 significantly correlated with the inhibition of apoptosis in serum-free culture. Moreover, picomolar concentrations (ng/ml) of recombinant Tat protein were able to upregulate Bcl-2 expression in serum-starved Jurkat cells and PBMC, suggesting that also extracellular Tat, actively released by infected cells, may play a significant role in suppressing apoptosis.