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

• Type of Material: Article
• Authors: Flora Mikaeloff, Karolinska Institutet; Sara Svensson Akusjarvi, Karolinska Institutet; George M Ikomey, University of Yaounde I; Shuba Krishnan, Karolinska Institutet; Maike Sperk, Karolinska Institutet; Soham Gupta, Karolinska Institutet; Gustavo Daniel Vega Magdaleno, University of Liverpool; Alejandra Escos, Karolinska Institutet; Emilia Lyonga, University of Yaounde I; Marie Claire Okomo, University of Yaounde I; Claude Tayou Tagne, University of Yaounde I; Hemalatha Babu, National Institute for Research in Tuberculosis, ICMR; Christian L Lorson, University of Missouri, Columbia; Ákos Vegvari, Karolinska Institutet; Akhil C Banerjea, National Institute of Immunology; Julianna Kele, Karolinska Institutet; Luke Elizabeth Hanna, National Institute for Research in Tuberculosis, ICMR; Kamal Singh, University of Missouri, Columbia; João Pedro de Magalhaes, University of Liverpool; Rui Benfeitas, Stockholm University; Ujjwal Neogi, Karolinska Institutet
• Language: English
• Date: 2022-01-11
• Publisher: NATURE PORTFOLIO
• Publication Version: Final Published Version
• Copyright Statement: © The Author(s) 2022
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1038/s42003-021-02985-3
• Title of Journal or Parent Work: COMMUNICATIONS BIOLOGY
• Volume: 5
• Issue: 1
• Start Page: 27
• End Page: 27
• Grant/Funding Information: 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; HIV-1-INFECTED MACROPHAGES; ACTIVATION; Life Sciences & Biomedicine - Other Topics; Biology; Science & Technology - Other Topics; Multidisciplinary Sciences; GLUCOSE
• Research Categories: Health Sciences, Pharmacology

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.