{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T18:58:46Z","timestamp":1790794726877,"version":"4.1.0"},"reference-count":64,"publisher":"American Society for Clinical Investigation","issue":"4","license":[{"start":{"date-parts":[[2024,2,22]],"date-time":"2024-02-22T00:00:00Z","timestamp":1708560000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MRC; NIH, NIAID, DAIDS; Wellcome Trust; ERC","award":["R01AI55182,MR\/M008614,MR\/K012037,AI144371,AI147778,SGL021\/1030,A2903,MRF-044-0004-F-GILL-C0823,ERC AdG 670930,100262"],"award-info":[{"award-number":["R01AI55182,MR\/M008614,MR\/K012037,AI144371,AI147778,SGL021\/1030,A2903,MRF-044-0004-F-GILL-C0823,ERC AdG 670930,100262"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2024,2,22]]},"abstract":"<jats:p>\n                    Dynamic regulation of cellular metabolism is important for maintaining homeostasis and can directly influence immune cell function and differentiation, including NK cell responses. Persistent HIV-1 infection leads to a state of chronic immune activation, NK cell subset redistribution, and progressive NK cell dysregulation. In this study, we examined the metabolic processes that characterize NK cell subsets in HIV-1 infection, including adaptive NK cell subpopulations expressing the activating receptor NKG2C, which expand during chronic infection. These adaptive NK cells exhibit an enhanced metabolic profile in HIV-1\n                    <jats:sup>\u2013<\/jats:sup>\n                    individuals infected with human cytomegalovirus (HCMV). However, the bioenergetic advantage of adaptive CD57\n                    <jats:sup>+<\/jats:sup>\n                    NKG2C\n                    <jats:sup>+<\/jats:sup>\n                    NK cells is diminished during chronic HIV-1 infection, where NK cells uniformly display reduced oxidative phosphorylation (OXPHOS). Defective OXPHOS was accompanied by increased mitochondrial depolarization, structural alterations, and increased DRP-1 levels promoting fission, suggesting that mitochondrial defects are restricting the metabolic plasticity of NK cell subsets in HIV-1 infection. The metabolic requirement for the NK cell response to receptor stimulation was alleviated upon IL-15 pretreatment, which enhanced mammalian target of rapamycin complex 1 (mTORC1) activity. IL-15 priming enhanced NK cell functionality to anti-CD16 stimulation in HIV-1 infection, representing an effective strategy for pharmacologically boosting NK cell responses.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.173099","type":"journal-article","created":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T14:00:38Z","timestamp":1708524038000},"source":"Crossref","is-referenced-by-count":30,"title":["IL-15 reprogramming compensates for NK cell mitochondrial dysfunction in HIV-1 infection"],"prefix":"10.1172","volume":"9","author":[{"given":"Elia","family":"Moreno-Cubero","sequence":"first","affiliation":[{"name":"Nuffield Department of Clinical Medicine and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aljawharah","family":"Alrubayyi","sequence":"additional","affiliation":[{"name":"Nuffield Department of Clinical Medicine 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