1. Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy
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You-Yuan Wang, Cheng Zhen, Wei Hu, Hui-Huang Huang, Yan-Jun Li, Ming-Ju Zhou, Jing Li, Yu-Long Fu, Peng Zhang, Xiao-Yu Li, Tao Yang, Jin-Wen Song, Xing Fan, Jun Zou, Si-Run Meng, Ya-Qin Qin, Yan-Mei Jiao, Ruonan Xu, Ji-Yuan Zhang, Chun-Bao Zhou, Jin-Hong Yuan, Lei Huang, Ming Shi, Liang Cheng, Fu-Sheng Wang, and Chao Zhang
- Subjects
Biology (General) ,QH301-705.5 - Abstract
Abstract CD8 + T cells are essential for long-lasting HIV-1 control and have been harnessed to develop therapeutic and preventive approaches for people living with HIV-1 (PLWH). HIV-1 infection induces marked metabolic alterations. However, it is unclear whether these changes affect the anti-HIV function of CD8 + T cells. Here, we show that PLWH exhibit higher levels of plasma glutamate than healthy controls. In PLWH, glutamate levels positively correlate with HIV-1 reservoir and negatively correlate with the anti-HIV function of CD8 + T cells. Single-cell metabolic modeling reveals glutamate metabolism is surprisingly robust in virtual memory CD8 + T cells (TVM). We further confirmed that glutamate inhibits TVM cells function via the mTORC1 pathway in vitro. Our findings reveal an association between metabolic plasticity and CD8 + T cell-mediated HIV control, suggesting that glutamate metabolism can be exploited as a therapeutic target for the reversion of anti-HIV CD8 + T cell function in PLWH.
- Published
- 2023
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