Activation of the transcription from the human immunodeficiency virus type 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 cell-to-cell contact between peripheral blood lymphocytes (PBLs) and 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 degree of cell-to-cell contact responsiveness was cell type dependent. In contrast, in transient transfection, the HIV-1-LTR was strongly induced by Tat expression in all cell types tested. This indicates that there are differences in the induction mechanism for these two stimuli, even though Tat protein has been previously reported to induce cell adhesion. Except for the PBLs/transfected cells interactions, the results also demonstrate that the cell-to-cell contact-induced HIV-1-LTR activation was highest after contact between autologous as compared to heterologous cells. Previous experiments have shown that, in HT29 cells, cell-to-cell contact activation of the HIV-1-LTR involved the NF-kappa B tandem binding site and activates DNA binding of the nuclear factor 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-LTR cell-to-cell contact activation. On the other hand, in the HT29 cell line, the NF-kappa B binding appeared to involve the RGD motif of the cell-binding domain, which indicates that a post-integrin receptor event could be implicated.
Institut de Chimie Biologique, Université de Provence, Marseille, France.
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E
Faure
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Lecine
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J
Imbert
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Champion
D002450:Cell Communication / Q000235:genetics*; D002478:Cells, Cultured; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D016325:HIV Long Terminal Repeat / Q000235:genetics*; D006801:Humans; D008214:Lymphocytes / Q000473:pathology; D015533:Transcriptional Activation; D014162:Transfection; D014407:Tumor Cells, Cultured