Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026918 (Mycobacterium)
 52,428 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-kappaB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells. 963 75

Worldwide, tuberculosis (TB) is the most frequent coinfection with human immunodeficiency virus-1 (HIV-1), and active TB enhances the progression of HIV-1 disease in dually infected subjects. In the microenvironment of Mycobacterium tuberculosis (MTB)-infected foci, where HIV-1-infected CD4 T-cells come into contact with MTB-infected macrophages, the direct interaction of the two cell types in the activation of latent HIV-1 may be important. In this study we sought to determine whether MTB-infected human primary mononuclear phagocytes-namely, alveolar macrophages (AMs) and their less mature blood precursors, monocytes-activate HIV-1 in a T-cell line stably transfected with an HIV-1 long terminal repeat (LTR) reporter construct (1G5 cells) and induce HIV-1 expression in T-cells from HIV-1-infected subjects. MTB-infected monocytes and AMs, and not Mycobacterium avium-infected cells, activated HIV-1 LTR in 1G5 cells in the presence and absence of HIV-1 tat. Transactivation of HIV-1 LTR by MTB-infected mononuclear phagocytes was mediated mainly by tumor necrosis factor-alpha. In AMs, but not monocytes, membrane tumor necrosis factor-alpha contributed to transactivation of HIV-1 LTR. MTB-infected MNs from 60% of HIV-infected subjects induced HIV-1 LTR in 1G5 cells as well. Furthermore, HIV-1 transcription was induced in autologous T-cells from 30% of the HIV-1-infected subjects. We therefore conclude that MTB-infected mononuclear phagocytes can transactivate HIV-1 in CD4 cells. Transactivation of latent HIV-1 in CD4 T-cells by MTB-infected mononuclear phagocytes may in part be responsible for increased HIV activity at sites of MTB infection during dual infection in vivo.
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PMID:Transactivation of human immunodeficiency virus-1 in T-cells by Mycobacterium tuberculosis-infected mononuclear phagocytes. 1532 5