Institute of Molecular Biology of Three Gorges University, Yichang, Hubei Province, China.
Angiology. 2010 Oct;61(7):669-78. doi: 10.1177/0003319710364215. Epub 2010 Jun 21.
Human immunodeficiency virus (HIV)-infected patients have increased rates of atherosclerotic cardiovascular diseases because the highly active antiretroviral therapy (HAART) decreased the morbidity and mortality of the disease. Endothelial dysfunction is possibly the most plausible link between HIV infection and related expression of cell adhesion molecules such as intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) on the endothelial cells. HIV-1 accessory protein negative regulate factor (Nef) has been shown to be very important for high virus replication and disease progression. Nef could upregulate the expression of ICAM-1 in the pathogenesis of HIV infection. Here, we provide evidence that the HIV-1 Nef can transcriptionally induce the expression of ICAM-1 in stable expressed Nef vascular endothelial cells. Nef-induced ICAM-1 upregulation requires the activation of the downstream kinase extracellular signal-regulated kinase (ERK). Flow cytometry (FCM) results showed that the percentage of ICAM-1 positive cells in Nef-expressed cells and control cells was (35.3% +/- 2.2%) and (12.5% +/- 0.8%), respectively (P < .01). Furthermore, inhibition of Nef activity by ERK mitogen-activated protein kinase (MAPK) inhibitor effectively blocked ICAM-1 upregulation, suggesting that ERK MAPK activation is an important initiating event in Nef-mediated ICAM-1 expression in Nef-expressed cells. These data demonstrate an important signaling event of Nef in HIV-1 pathogenesis.
人类免疫缺陷病毒（HIV）感染患者发生动脉粥样硬化性心血管疾病的风险增加，这是因为高效抗逆转录病毒疗法（HAART）降低了疾病的发病率和死亡率。内皮功能障碍可能是 HIV 感染与细胞间黏附分子 1（ICAM-1）和血管细胞黏附分子 1（VCAM-1）等相关细胞黏附分子表达之间最合理的联系。已经表明，HIV-1 辅助蛋白负调节因子（Nef）对于高病毒复制和疾病进展非常重要。Nef 可上调 HIV 感染发病机制中 ICAM-1 的表达。在这里，我们提供的证据表明，HIV-1 Nef 可以在稳定表达 Nef 的血管内皮细胞中转录诱导 ICAM-1 的表达。Nef 诱导的 ICAM-1 上调需要下游激酶细胞外信号调节激酶（ERK）的激活。流式细胞术（FCM）结果显示，Nef 表达细胞和对照细胞中 ICAM-1 阳性细胞的百分比分别为（35.3% +/- 2.2%）和（12.5% +/- 0.8%）（P <.01）。此外，ERK 丝裂原活化蛋白激酶（MAPK）抑制剂抑制 Nef 活性可有效阻断 ICAM-1 的上调，表明 ERK MAPK 激活是 Nef 介导的 Nef 表达细胞中 ICAM-1 表达的重要起始事件。这些数据表明 Nef 在 HIV-1 发病机制中具有重要的信号事件。
