Medical School of Chinese PLA, Beijing, China.
Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
Commun Biol. 2023 Jul 7;6(1):696. doi: 10.1038/s42003-023-04975-z.
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.
CD8+T 细胞对于长期控制 HIV-1 至关重要，已被用于开发针对 HIV-1 感染者（PLWH）的治疗和预防方法。HIV-1 感染会引起显著的代谢改变。然而，目前尚不清楚这些变化是否会影响 CD8+T 细胞的抗 HIV 功能。在这里，我们发现 PLWH 的血浆谷氨酸水平高于健康对照组。在 PLWH 中，谷氨酸水平与 HIV-1 储存库呈正相关，与 CD8+T 细胞的抗 HIV 功能呈负相关。单细胞代谢建模显示，虚拟记忆 CD8+T 细胞（TVM）中的谷氨酸代谢惊人地稳健。我们进一步证实，谷氨酸通过体外 mTORC1 通路抑制 TVM 细胞的功能。我们的研究结果揭示了代谢可塑性与 CD8+T 细胞介导的 HIV 控制之间的关联，表明谷氨酸代谢可作为恢复 PLWH 抗 HIV CD8+T 细胞功能的治疗靶点。
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