The Systems Virology Lab, Division of Clinical Microbiology, Department of Laboratory Medicine, Karolinska Institute, ANA Futura, Campus Flemingsberg, Stockholm, Sweden.
Center for the Study and Control of Communicable Diseases (CSCCD), Faculty of Medicine and Biomedical Sciences, University of Yaoundé 1, P.O. Box. 8445, Yaoundé, Cameroon.
Commun Biol. 2022 Jan 11;5(1):27. doi: 10.1038/s42003-021-02985-3.
Despite successful combination antiretroviral therapy (cART), persistent low-grade immune activation together with inflammation and toxic antiretroviral drugs can lead to long-lasting metabolic flexibility and adaptation in people living with HIV (PLWH). Our study investigated alterations in the plasma metabolic profiles by comparing PLWH on long-term cART(>5 years) and matched HIV-negative controls (HC) in two cohorts from low- and middle-income countries (LMIC), Cameroon, and India, respectively, to understand the system-level dysregulation in HIV-infection. Using untargeted and targeted LC-MS/MS-based metabolic profiling and applying advanced system biology methods, an altered amino acid metabolism, more specifically to glutaminolysis in PLWH than HC were reported. A significantly lower level of neurosteroids was observed in both cohorts and could potentiate neurological impairments in PLWH. Further, modulation of cellular glutaminolysis promoted increased cell death and latency reversal in pre-monocytic HIV-1 latent cell model U1, which may be essential for the clearance of the inducible reservoir in HIV-integrated cells.
尽管成功地进行了联合抗逆转录病毒治疗（cART），但持续性低度免疫激活以及炎症和有毒的抗逆转录病毒药物会导致艾滋病毒感染者（PLWH）长期保持代谢灵活性和适应性。我们的研究通过比较来自中低收入国家（LMIC）喀麦隆和印度的两个队列中接受长期 cART（>5 年）的 PLWH 和匹配的 HIV 阴性对照（HC），调查了血浆代谢谱的变化，以了解 HIV 感染中的系统水平失调。我们使用非靶向和靶向 LC-MS/MS 代谢组学分析，并应用先进的系统生物学方法，报告了 PLWH 中氨基酸代谢的改变，更具体地说是谷氨酰胺分解代谢的改变，而 HC 则没有。我们还观察到两个队列中神经甾体水平显著降低，这可能会加重 PLWH 的神经损伤。此外，细胞谷氨酰胺分解代谢的调节促进了前单核细胞 HIV-1 潜伏细胞模型 U1 中细胞死亡和潜伏逆转的增加，这对于清除 HIV 整合细胞中的诱导性储库可能是必要的。
