Department of Immunology/Microbiology, Rush University Medical Center, Chicago, IL 60612, USA.
Virology. 2013 Sep 1;443(2):375-83. doi: 10.1016/j.virol.2013.05.027. Epub 2013 Jun 12.
Human Immunodeficiency virus type 1 (HIV-1) disproportionately affects women, accounting for > 50% of new HIV infections in adults worldwide. While multiple mechanisms may contribute to a greater degree of HIV infection in women than men, we evaluated the direct effect of 17β-estradiol, the most bioactive form of estrogen in women, on HIV replication in peripheral blood mononuclear cells (PBMCs). We demonstrate that 17β-estradiol, in an ERα dependent manner, inhibits HIV replication by activating β-catenin signaling. Specifically, we show for the first time that 17β-estradiol induces a complex formation between ERα and β-catenin which tether on the HIV LTR at -143nt site from +1 start site of HIV transcription to repress HIV promoter activity. These studies define a role of 17β-estradiol in inhibiting HIV replication which may impact HIV pathogenesis in women and add to a growing list of viruses that are inhibited by 17β-estradiol through ERα engagment.
人类免疫缺陷病毒 1 型（HIV-1）在女性中不成比例地流行，占全球成年人新感染 HIV 的比例>50%。虽然有多种机制可能导致女性比男性更容易感染 HIV，但我们评估了女性中生物活性最强的雌激素 17β-雌二醇对周围血单核细胞（PBMC）中 HIV 复制的直接影响。我们证明，17β-雌二醇通过激活β-连环蛋白信号以 ERα 依赖性方式抑制 HIV 复制。具体来说，我们首次表明，17β-雌二醇诱导 ERα 和β-连环蛋白之间形成复合物，该复合物与 HIV LTR 在 -143nt 位点结合，该位点位于 HIV 转录的+1 起始位点到 HIV 启动子活性的抑制。这些研究定义了 17β-雌二醇在抑制 HIV 复制中的作用，这可能会影响女性的 HIV 发病机制，并增加越来越多的通过 ERα 参与被 17β-雌二醇抑制的病毒的清单。
