ACTIVATION OF THE TRANSCRIPTION FROM THE HUMAN-IMMUNODEFICIENCY-VIRUSTYPE-1 (HIV-1) LONG TERMINAL REPEAT BY AUTOLOGOUS AND HETEROLOGOUS CELL-TO-CELL CONTACT

Recent studies have demonstrated that the activation of HIV-1 provirus and of the Long Terminal Repeat of HIV-1 (HIV-1-LTR) may occur upon c ell cell-to-cell contact between peripheral blood lymphocytes (PBLs) a nd infected or transfected (HT29) human colonic carcinoma cells. Using transient or stable transfections, we ascertained that the HIV-1 LTR was up-regulated by cell-to-cell contact in various cell lines. The de gree of cell-to-cell contact responsiveness was cell type dependent. I n constrast, in transient transfection, the HIV-1-LTR was strongly ind uced by Tat expression in all cell types tested. This indicates that t here are differences in the induction mechanism for these two stimuli, even though Tar protein has been previously reported to induce cell a dhesion. Except for the PBLs/transfected cells interactions, the resul ts also demonstrate that the cell-to-cell contact-induced HIV-1-LTR ac tivation was highest after contact between autologous as compared to h eterologous cells. Previous experiments have shown that, in HT29 cells , cell-to-cell contact activation of the HIV-1-LTR involved the NF-kap pa B tandem binding site and activates DNA binding of the nuclear fact or NF-kappa B. In this work, we show that in a stably transfected cell line, the principal enhancer element was also involved in the HIV-1-L TR cell-to-cell contact activation. On the other hand, in the HT29 cel l line, the NF-kappa B binding appeared to involve the RGD motif of th e cell-binding domain, which indicates that a post-integrin receptor e vent could be implicated.