The Lipophosphoglycan of Leishmania donovani Up-Regulates HIV-1 Transcription in T Cells Through the Nuclear Factor-κB Elements

• Published in: The Journal of immunology (1950) 1998-03, Vol.160 (6), p.2881-2888
• Main Authors: Bernier, Richard, Barbeau, Benoı̂t, J. Tremblay, Michel, Olivier, Martin
• Format: Article
• Language: English
• ISSN: 0022-1767; 1550-6606
• DOI: 10.4049/jimmunol.160.6.2881

We have recently demonstrated that the parasite Leishmania donovani and its surface molecule, lipophosphoglycan (LPG), can activate HIV-1 replication in monocytoid cells. Our present interest was to determine whether LPG could also up-regulate HIV-1 transcription in T cells. Using a CD4-positive human lymphoid T cell line (1G5) containing a stably integrated HIV-1 long terminal repeat (LTR)-luciferase construct, we found that LPG is a potent inducer of HIV-1 LTR activity. Treatment of 1G5 cells with signaling antagonists revealed that protein tyrosine kinase- and protein kinase A-dependent pathways were actively participating in the LPG-induced enhancement of HIV-1 LTR-driven activity. Transfection of Jurkat E6.1 cells with plasmids containing wild-type and nuclear factor-κB (NF-κB)-mutated HIV-1 LTR-luciferase constructs has suggested a role for NF-κB binding sites in the LPG-mediated induction of HIV-1 LTR activity. An LPG-induced binding factor specific to the NF-κB consensus sequences could be observed using electrophoretic mobility shift assay. Finally, transfection experiments performed with a vector containing HIV-1 κB binding sites only showed similar LPG-mediated induction, which was abrogated by sodium salicylate, a known NF-κB inhibitor. We thus demonstrate that the LPG-mediated induction of HIV-1 LTR activity in T cells involves several second messengers culminating in activation of HIV-1 LTR-driven transcription via NF-κB-binding consensus sequences. In conclusion, these results reinforce the idea that L. donovani is a putative cofactor in HIV-1 pathogenesis.