Bacterial lipopolysaccharide activates HIV long terminal repeat through toll-like receptor 4
Bacterial lipopolysaccharide activates HIV long terminal repeat through toll-like receptor 4
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DOI：
10.4049/jimmunol.166.4.2342
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发表时间：
2001-02-15
影响因子：
4.4
通讯作者：
Arditi, M
中科院分区：
文献类型：
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作者：
Equils, O;Faure, E;Arditi, M
在HIV感染的患者中，已知细菌和病毒的并发感染诱导HIV复制，如通过血浆HIV RNA水平的增加所评估的。在本研究中，我们确定了肠细菌LPS诱导HIV转录的细胞表面受体和分子机制。用HIV-长末端重复序列（LTR）-荧光素酶构建体转染人真皮微血管内皮细胞（HMEC），随后用纯化的细菌LPS刺激。我们的研究表明，人Top样受体4（TLR 4）介导LPS诱导的NF-κ B和HIV-LTR激活HMEC通过IL-1。信号分子，即髓样分化蛋白、UL-1 R相关激酶、TNFR相关因子和NF-κ B诱导激酶，来自LPS低应答C3 H/HeJ小鼠的HMEC与HIV-LTR-荧光素酶和TLR 4 cDNA的共转染消除了LPS诱导的HIV转录，如使用IL-1信号分子的显性阴性突变体一样，用缺乏NF-κ B结合位点的HIV-LTR突变体转染HMEC或用NF-κ B途径的化学抑制剂预处理细胞也阻断了LPS诱导的HIV-LTR反式激活，这些数据支持TLR 4通过IL-1信号分子介导肠细菌LPS诱导的HIV转录的结论，并且NF-κ B活化在HIV-LTR反式激活中起重要作用。
In HIV-infected patients, concurrent infections with bacteria and viruses are known to induce HIV replication as assessed by increases in plasma HIV RNA levels, In the present study we determined the cell surface receptor and molecular mechanisms of enterobacterial LPS-induced HIV transcription. Human dermal microvessel endothelial cells (HMEC) were transfected with an HIV-long terminal repeat (LTR)-luciferase construct and subsequently stimulated with purified bacterial LPS. Our studies demonstrate that human Top-like receptor 4 (TLR4) mediates LPS-induced NF-kappaB and HIV-LTR activation in HMEC through IL-1. signaling molecules, namely myeloid differentiation protein, UL-1R-associated kinase, TNFR-associated factor, and NF-KB-inducing kinase, Cotransfection of HMEC with HIV-LTR-luciferase and TLR4 cDNA from LPS-hyporesponsive C3H/HeJ mice abrogates LPS-induced HIV transcription as does the use of dominant-negative mutants of the IL-1 signaling molecules, Transfection of HMEC with an HIV-LTR-mutant that lacks the NF-kappaB binding site or pretreatment of cells with chemical inhibitors of the NF-kappaB pathway also blocked LPS-induced HIV-LTR transactivation, These data support the conclusion that TLR4 mediates enterobacterial LPS-induced HIV transcription via IL-I signaling molecules and NF-kappaB activation plays an important role in HIV-LTR transactivation.