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Author Notes:

Ujjwal Neogi, Email: ujjwal.neogi@ki.se

Conceptualization and study designing: U.N., Clinical data, and biobank: G.M.I., E.L., M.C.O, C.T.T., H.B. L.E.H., Methodology: F.M., R.B., J.P.d.M., and U.N., Formal analysis (bioinformatics): F.M. and G.D.V.M. and R.B., Formal analysis (experimental): S.S.A., S.K., M.S., A.E., A.V., and S.G., Supervision: R.B., J.P.d.M., and U.N., Resources: U.N. Writing (original draft): F.M., S.S.A, S.K., M.S., and U.N. Writing (review and editing): R.B., G.D.V.M., A.C.B, J.K., K.S., C.L.L., and J.P.d.M., Visualization: F.M., S.S.A, S.K. and U.N., Project administration: G.M.I., L.E.H., and U.N. Funding acquisition: U.N. All authors discussed the results, commented, and approved the final version of the manuscript.

We thank all the study subjects for their participation. Authors acknowledge support from the Proteomics Biomedicum; Karolinska Institute, Solna, for LC-MS/MS analysis. Swedish Metabolomics Centre, Umeå, Sweden is acknowledged for targeted metabolic profiling.

C.L.L. is the co-founder and chief scientific officer for Shift Pharmaceuticals. The remaining authors declare no competing interests.

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Research Funding:

The study is supported by the Swedish Research Council (2017-01330, 2018-06156 and 2021-01756), Karolinska Institutet Stiftelser och Fonder (2020-01554), and Åke Wiberg Stiftelse grant (M18-0021). Swedish Physicians Against AIDS Foundation (FOb20170004) and Jeanssons Stiftelser (JS2016–0185) to UN. MS acknowledges the support received from the Swedish Physicians Against AIDS Foundation (FOa2019-0020). SG acknowledges support from the Swedish Research Council Establishment grant (2021-03035), the Center for Medical Innovation grant (CIMED-FoUI-093304), Karolinska Institutet Stiftelser och Fonder (2020-02153), and Åke Wiberg Stiftelse grant (M20-0220).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Biology
  • Multidisciplinary Sciences
  • Life Sciences & Biomedicine - Other Topics
  • Science & Technology - Other Topics
  • HIV-1-INFECTED MACROPHAGES
  • GLUCOSE
  • ACTIVATION

Trans cohort metabolic reprogramming towards glutaminolysis in long-term successfully treated HIV-infection

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Journal Title:

COMMUNICATIONS BIOLOGY

Volume:

Volume 5, Number 1

Publisher:

, Pages 27-27

Type of Work:

Article | Final Publisher PDF

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.

Copyright information:

© The Author(s) 2022

This is an Open Access work distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons.org/licenses/by/4.0/rdf).
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