Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells

• Published in: Journal of general virology 1998-06, Vol.79 (6), p.1353-1361
• Main Authors: Bernier, R, Barbeau, B, Olivier, M, Tremblay, MJ
• Format: Article
• Language: English
• Subjects: AIDS/HIV; Binding Sites; Cyclic AMP-Dependent Protein Kinases - metabolism; Gene Expression Regulation, Viral; HIV Long Terminal Repeat; HIV-1 - genetics; Humans; Jurkat Cells; Lipopolysaccharides - metabolism; Lipopolysaccharides - pharmacology; Mannose; Mycobacterium tuberculosis - metabolism; NF-kappa B - metabolism; Protein Kinase C - metabolism; Protein-Tyrosine Kinases - metabolism; T-Lymphocytes - virology; Transcription, Genetic; Tumor Necrosis Factor-alpha - metabolism; Up-Regulation
• ISSN: 0022-1317; 1465-2099
• DOI: 10.1099/0022-1317-79-6-1353

R Bernier, B Barbeau, M Olivier and MJ Tremblay Departement de Biologie Medicale, Faculte de Medecine, Universite Laval, Ste-Foy, Quebec, Canada. Tuberculosis has emerged as an epidemic, extended by the large number of individuals infected with human immunodeficiency virus type 1 (HIV- 1). The major goal of this study was to determine whether the mycobacterial cell wall component mannose-capped lipoarabinomannan (ManLAM) of Mycobacterium tuberculosis (M. tuberculosis) could activate transcription of HIV-1 in T cells with the use of an in vitro cell culture system. These experiments are of prime importance considering that CD4-expressing T lymphocytes represent the major virus reservoir in the peripheral blood of infected individuals. Using the 1G5 cell line harbouring the luciferase reporter gene under the control of the HIV-1 LTR, it was first found that culture protein filtrates (CFP) from M. tuberculosis or purified ManLAM could activate HIV-1 LTR-dependent gene expression unlike similarly prepared CFP extracts devoid of ManLAM. The implication of protein tyrosine kinase(s), protein kinase A and/or protein kinase C was highlighted by the abrogation of the ManLAM- mediated activation of HIV-1 LTR-driven gene expression using herbimycin A and H7. It was also determined, using electrophoresis mobility shift assays, that M. tuberculosis ManLAM led to the nuclear translocation of the transcription factor NF-kappaB. M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type, but not the kappaB-mutated, HIV-1 LTR region. Finally, the ManLAM-mediated activation of HIV-1 LTR transcription was found to be independent of the autocrine or paracrine action of endogenous TNF-alpha. The results suggest that M. tuberculosis can upregulate HIV-1 expression in T cells and could thus have the potential to influence the pathogenesis of HIV-1 infection.