Palmer Clovis S, Duette Gabriel A, Wagner Marc C E, Henstridge Darren C, Saleh Suah, Pereira Candida, Zhou Jingling, Simar David, Lewin Sharon R, Ostrowski Matias, McCune Joseph M, Crowe Suzanne M
Centre for Biomedical Research, Burnet Institute, Melbourne, Australia.
Department of Infectious Diseases, Monash University, Melbourne, Australia.
FEBS Lett. 2017 Oct;591(20):3319-3332. doi: 10.1002/1873-3468.12843. Epub 2017 Oct 11.
High glucose transporter 1 (Glut1) surface expression is associated with increased glycolytic activity in activated CD4+ T cells. Phosphatidylinositide 3-kinases (PI3K) activation measured by p-Akt and OX40 is elevated in CD4+Glut1+ T cells from HIV+ subjects. TCR engagement of CD4+Glut1+ T cells from HIV+ subjects demonstrates hyperresponsive PI3K-mammalian target of rapamycin signaling. High basal Glut1 and OX40 on CD4+ T cells from combination antiretroviral therapy (cART)-treated HIV+ patients represent a sufficiently metabolically active state permissive for HIV infection in vitro without external stimuli. The majority of CD4+OX40+ T cells express Glut1, thus OX40 rather than Glut1 itself may facilitate HIV infection. Furthermore, infection of CD4+ T cells is limited by p110γ PI3K inhibition. Modulating glucose metabolism may limit cellular activation and prevent residual HIV replication in 'virologically suppressed' cART-treated HIV+ persons.
高葡萄糖转运蛋白1（Glut1）的表面表达与活化的CD4+T细胞中糖酵解活性增加相关。通过p-Akt和OX40检测到的磷脂酰肌醇3-激酶（PI3K）活化在HIV+受试者的CD4+Glut1+T细胞中升高。HIV+受试者的CD4+Glut1+T细胞的TCR参与显示出对PI3K-雷帕霉素哺乳动物靶标信号的高反应性。来自接受联合抗逆转录病毒治疗（cART）的HIV+患者的CD4+T细胞上的高基础Glut1和OX40代表了一种足够代谢活跃的状态，在没有外部刺激的情况下允许HIV在体外感染。大多数CD4+OX40+T细胞表达Glut1，因此OX40而非Glut1本身可能促进HIV感染。此外，CD4+T细胞的感染受到p110γ PI3K抑制的限制。调节葡萄糖代谢可能会限制细胞活化并防止在“病毒学抑制”的接受cART治疗的HIV+人群中残留HIV复制。
