Sawaya B E, Rohr O, Aunis D, Schaeffer E
Unité 338 INSERM, 5, rue Blaise Pascal, 67084 Strasbourg Cedex, France.
J Biol Chem. 1996 Sep 13;271(37):22895-900. doi: 10.1074/jbc.271.37.22895.
Infection of cells of the central nervous system by the human immunodeficiency virus type-1 (HIV-1) leads to HIV-1-associated neuropathology. Recent studies have demonstrated the importance of long terminal repeat (LTR) binding sites in determining the pathogenicity of HIV. Here we have investigated the presence and the functional role of transcription factors that have the potential to interact, directly or indirectly, with the nuclear receptor-responsive element in the LTR of HIV-1, in different human cell lines of the brain. Cotransfection experiments showed that in oligodendroglioma TC-620 cells, the retinoic acid receptor and the retinoid X receptor activate LTR-driven transcription in the absence of ligand. Addition of all-trans- or 9-cis-retinoic acid reverses this effect. In contrast, in astrocytoma, neuronal, and microglial cells, no significant effect of the retinoid acid pathway was detected. This retinoid response is mediated by distinct molecular interactions in the lymphotropic LAI and the neurotropic JR-CSF HIV-1 strains. Moreover, retinoid receptors were found to antagonize the chicken ovalbumin upstream promoter transcription factor- as well as the c-JUN-mediated LTR transactivation. Our findings demonstrate the importance of the retinoic acid signaling pathway and of cross-coupling interactions in the repression of HIV-1 LTR gene expression.
1型人类免疫缺陷病毒（HIV-1）感染中枢神经系统细胞会导致与HIV-1相关的神经病理学。最近的研究表明长末端重复序列（LTR）结合位点在决定HIV致病性方面的重要性。在此，我们研究了在不同的人类脑细胞系中，有可能直接或间接与HIV-1 LTR中的核受体反应元件相互作用的转录因子的存在情况及其功能作用。共转染实验表明，在少突胶质细胞瘤TC-620细胞中，视黄酸受体和视黄醇X受体在无配体的情况下激活LTR驱动的转录。添加全反式或9-顺式视黄酸可逆转这种效应。相比之下，在星形细胞瘤、神经元和小胶质细胞中，未检测到视黄酸途径的显著影响。这种视黄酸反应是由嗜淋巴细胞的LAI株和嗜神经的JR-CSF HIV-1株中不同的分子相互作用介导的。此外，发现视黄酸受体可拮抗鸡卵清蛋白上游启动子转录因子以及c-JUN介导的LTR反式激活。我们的研究结果证明了视黄酸信号通路以及交叉偶联相互作用在抑制HIV-1 LTR基因表达中的重要性。
