Mikaeloff, Flora, Akusjarvi, Sara Svensson, Ikomey, George Mondinde, Krishnan, Shuba, Sperk, Maike, Gupta, Soham, Magdaleno, Gustavo Daniel Vega, Escos, Alejandra, Lyonga, Emilia, Okomo, Marie Claire et al (show 11 more authors)
(2022)
Trans cohort metabolic reprogramming towards glutaminolysis in long-term successfully treated HIV-infection.
COMMUNICATIONS BIOLOGY, 5 (1).
27-.
Abstract
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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | Cells, Cultured, Humans, HIV Infections, Glutamine, Anti-HIV Agents, Systems Biology, Energy Metabolism, Glycolysis, Adult, Middle Aged, Female, Male, Metabolomics, Metabolome |
| Divisions: | Faculty of Health and Life Sciences Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences |
| Depositing User: | Symplectic Admin |
| Date Deposited: | 06 Feb 2024 11:10 |
| Last Modified: | 06 Feb 2024 11:10 |
| DOI: | 10.1038/s42003-021-02985-3 |
| Open Access URL: | https://doi.org/10.1038/s42003-021-02985-3 |
| Related URLs: | |
| URI: | https://livrepository.liverpool.ac.uk/id/eprint/3178499 |
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