Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy

  • Commun Biol. 2023 Jul 7;6(1):696. doi: 10.1038/s42003-023-04975-z.
You-Yuan Wang  #  1  2 ,  Cheng Zhen  #  2 ,  Wei Hu  #  3 ,  Hui-Huang Huang  2 ,  Yan-Jun Li  4 ,  Ming-Ju Zhou  2 ,  Jing Li  2 ,  Yu-Long Fu  2 ,  Peng Zhang  2 ,  Xiao-Yu Li  2 ,  Tao Yang  1  2 ,  Jin-Wen Song  1  2 ,  Xing Fan  2 ,  Jun Zou  4 ,  Si-Run Meng  4 ,  Ya-Qin Qin  4 ,  Yan-Mei Jiao  2 ,  Ruonan Xu  1  2 ,  Ji-Yuan Zhang  2 ,  Chun-Bao Zhou  2 ,  Jin-Hong Yuan  2 ,  Lei Huang  2 ,  Ming Shi  1  2 ,  Liang Cheng  5 ,  Fu-Sheng Wang  6  7  8 ,  Chao Zhang  9  10  11
Affiliations
  • 1. Medical School of Chinese PLA, Beijing, China.
  • 2. Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China.
  • 3. Department of Emergency, Fifth Medical Center of Chinese PLA Hospital, Beijing, China.
  • 4. Guangxi AIDS Clinical Treatment Centre, The Fourth People's Hospital of Nanning, Nanning, China.
  • 5. Medical Research Institute, Frontier Science Center of Immunology and Metabolism, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan, China.
  • 6. Medical School of Chinese PLA, Beijing, China. [email protected].
  • 7. Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. [email protected].
  • 8. Guangxi AIDS Clinical Treatment Centre, The Fourth People's Hospital of Nanning, Nanning, China. [email protected].
  • 9. Medical School of Chinese PLA, Beijing, China. [email protected].
  • 10. Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. [email protected].
  • 11. Guangxi AIDS Clinical Treatment Centre, The Fourth People's Hospital of Nanning, Nanning, China. [email protected].
  • # Contributed equally.
PMID: 37419968 DOI: 10.1038/s42003-023-04975-z
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.

Products