Estrogen stimulates transcription of human immunodeficiency virus type 1 (HIV-1)
Estrogen stimulates transcription of human immunodeficiency virus type 1 (HIV-1)
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DOI：
10.1016/j.intimp.2005.07.017
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发表时间：
2006-02-01
影响因子：
5.6
通讯作者：
Onozaki, K
中科院分区：
文献类型：
--
作者：
Katagiri, D;Hayashi, H;Onozaki, K
人类免疫缺陷病毒（human immunodeficiency virus，HIV）前病毒的基因表达是病毒复制的关键步骤.在这里，我们研究了17 β-雌二醇（E2）在HIV-1转录中的潜在作用。瞬时荧光素酶表达研究显示，当HEK 293细胞与雌激素受体α（ERU）共转染时，E2激活了HIV-LTR报告基因，但ER β表达质粒不激活。这种E2效应被ER的特异性拮抗剂ICI 182，780所消除，表明它是由ER α介导的。突变分析表明，HIV-1 LTR的Sp1结合位点而非核因子-κ B（NF-κ B）结合位点是E2效应的关键。此外，E2不能诱导NF-κ B的DNA结合活性，而E2可以增强Sp1的DNA结合和转录活性。这些研究结果表明，雌激素通过增强Sp1 DNA结合和转录活性，通过ER α对HIV-1复制的贡献。(c)2005 Elsevier B. V.保留所有权利。
Gene expression from human immunodeficiency virus (HIV) provirus is a crucial step for the viral replication. Here we examined a potential role of 17 beta-estradiol (E2) in HIV-1 transcription. Transient luciferase expression studies revealed that E2 activated HIV-LTR reporter gene in HEK293 cells when the cells were co-transfected with estrogen receptor alpha (ERU) but not ER beta expression plasmid. This E2 effect was abrogated by a specific antagonist to ER, ICI 182,780, indicating that it was mediated by ER alpha. Mutation analysis revealed that Sp1 binding site but not nuclear factor-kappa B (NF-kappa B) binding site of HIV-1 LTR is critical to the E2 effect. In addition, whereas E2 could not induce DNA-binding activity of NF-kappa B, E2 could augment both Sp1 DNA-binding and transcriptional activity. These findings suggest a contribution of estrogen for HIV-1 replication through ER alpha by augmenting Sp1 DNA-binding and transcriptional activity. (c) 2005 Elsevier B.V. All rights reserved.