1.North Shore University Hospital, 100 Community Drive, Great Neck, NY 11021; E-mail
J Leukoc Biol. 2013 Oct;94(4):769-77. doi: 10.1189/jlb.0313142. Epub 2013 Aug 2.
It is well known that patients with HIV are prone to diabetes mellitus because of the side effects of HARRT. However, whether high glucose affects the HIV infection of T cells is not clear. Recent studies have shown that upregulation of GLUT-1 renders T cells susceptible to HIV infection. We hypothesized that hyperglycemia has the potential to increase HIV infection by enhancing its entry into immune cells. The effect of high glucose on HIV entry into T cells (Jurkat cells and PBMCs) and the mechanisms involved were investigated. High glucose significantly enhanced HIV entry, which was associated with increased T-cell expression of CXCR4. However, T cells with silenced HIF-1α displayed attenuated expression of CXCR4, whereas T cells with silenced CXCR4 showed decreased HIV entry in a high-glucose milieu. On the one hand, high glucose stimulated T-cell ROS generation, and H(2)O(2) at low concentrations enhanced the entry of HIV into T cells. On the other hand, inhibition of ROS not only attenuated high-glucose-mediated T-cell expression of CXCR4 and HIF-1α but also mitigated T-cell HIV entry in a high-glucose milieu. In our study, high glucose enhanced HIV entry into T cells by increasing expression of CXCR4 and HIF-1α.
众所周知，由于抗逆转录病毒疗法（HARRT）的副作用，HIV 患者易患糖尿病。然而，高血糖是否会影响 T 细胞感染 HIV 尚不清楚。最近的研究表明，GLUT-1 的上调使 T 细胞容易感染 HIV。我们假设高血糖有可能通过增强其进入免疫细胞来增加 HIV 感染的可能性。研究了高葡萄糖对 T 细胞（Jurkat 细胞和 PBMC）中 HIV 进入的影响及其涉及的机制。高葡萄糖显著增强了 HIV 的进入，这与 T 细胞中 CXCR4 的表达增加有关。然而，沉默 HIF-1α 的 T 细胞显示出 CXCR4 的表达减弱，而沉默 CXCR4 的 T 细胞在高葡萄糖环境中显示出 HIV 进入减少。一方面，高葡萄糖刺激 T 细胞 ROS 的产生，低浓度的 H2O2 增强了 HIV 进入 T 细胞。另一方面，抑制 ROS 不仅减弱了高葡萄糖介导的 T 细胞 CXCR4 和 HIF-1α 的表达，而且减轻了高葡萄糖环境中 T 细胞的 HIV 进入。在我们的研究中，高葡萄糖通过增加 CXCR4 和 HIF-1α 的表达来增强 HIV 进入 T 细胞。
