Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-κB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells
Mycobacterium tuberculosis mannose-capped lipoarabinomannan can induce NF-κB-dependent activation of human immunodeficiency virus type 1 long terminal repeat in T cells
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DOI：
10.1099/0022-1317-79-6-1353
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发表时间：
1998-06-01
影响因子：
3.8
通讯作者：
Tremblay, MJ
中科院分区：
文献类型：
--
作者：
Bernier, R;Barbeau, B;Tremblay, MJ
结核病已成为一种流行病，并因大量感染 1 型人类免疫缺陷病毒 (HIV-1) 的个体而扩大。本研究的主要目标是确定结核分枝杆菌 (M. tuberculosis) 的分枝杆菌细胞壁成分甘露糖加帽的阿拉伯脂甘露聚糖 (ManLAM) 是否可以使用体外细胞培养系统激活 T 细胞中 HIV-1 的转录。考虑到以下因素，这些实验至关重要：表达 CD4 的 T 淋巴细胞是感染者外周血中的主要病毒库。使用在 HIV-1 LTR 控制下含有荧光素酶报告基因的 1G5 细胞系，首次发现来自结核分枝杆菌或纯化的 ManLAM 的培养蛋白滤液 (CFP) 可以激活 HIV-1 LTR 依赖性基因表达，这与类似制备的不含 ManLAM 的 CFP 提取物不同。通过使用除草霉素 A 和 H7 消除 ManLAM 介导的 HIV-1 LTR 驱动基因表达的激活，突显了蛋白酪氨酸激酶、蛋白激酶 A 和/或蛋白激酶 C 的含义。使用电泳迁移率变动分析还确定，结核分枝杆菌 ManLAM 导致转录因子 NF-κ B 的核转位，结核分枝杆菌 ManLAM 导致明显诱导最后，发现ManLAM介导的HIV-1 LTR转录激活不依赖于内源性TNF-α的自分泌或旁分泌作用。结果表明，结核分枝杆菌可以上调 T 细胞中的 HIV-1 表达，因此有可能影响 HIV-1 感染的发病机制。
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-kappa B, M. tuberculosis ManLAM resulted in clear induction of the luciferase gene placed under the control of the wild-type, but not the KB-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.