2. Academic Validation
  3. Elevated glutamate impedes anti-HIV-1 CD8 + T cell responses in HIV-1-infected individuals on antiretroviral therapy

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

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. fswang302@163.com.
  • 7 Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. fswang302@163.com.
  • 8 Guangxi AIDS Clinical Treatment Centre, The Fourth People's Hospital of Nanning, Nanning, China. fswang302@163.com.
  • 9 Medical School of Chinese PLA, Beijing, China. zhangch302@163.com.
  • 10 Department of Infectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, National Clinical Research Center for Infectious Diseases, Beijing, China. zhangch302@163.com.
  • 11 Guangxi AIDS Clinical Treatment Centre, The Fourth People's Hospital of Nanning, Nanning, China. zhangch302@163.com.
  • # 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.

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