{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,25]],"date-time":"2026-08-25T23:41:01Z","timestamp":1787701261737,"version":"build-2784847793"},"reference-count":52,"publisher":"Public Library of Science (PLoS)","issue":"1","license":[{"start":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T00:00:00Z","timestamp":1736467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100016036","name":"Health~Holland","doi-asserted-by":"publisher","award":["LSHM19101"],"award-info":[{"award-number":["LSHM19101"]}],"id":[{"id":"10.13039\/100016036","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007553","name":"Aids Fonds","doi-asserted-by":"publisher","award":["P-44802"],"award-info":[{"award-number":["P-44802"]}],"id":[{"id":"10.13039\/100007553","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Health~Holland\/AMC","award":["2019\/1167"],"award-info":[{"award-number":["2019\/1167"]}]}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>Identifying cellular and molecular mechanisms maintaining HIV-1 latency in the viral reservoir is crucial for devising effective cure strategies. Here we developed an innovative flow cytometry-fluorescent <jats:italic>in situ<\/jats:italic> hybridization (flow-FISH) approach for direct <jats:italic>ex vivo<\/jats:italic> reservoir detection without the need for reactivation using a combination of probes detecting abortive and elongated HIV-1 transcripts. Our flow-FISH assay distinguished between HIV-1-infected CD4+ T cells expressing abortive or elongated HIV-1 transcripts in PBMC from untreated and ART-treated PWH from the Amsterdam Cohort Studies. This flow-FISH method was employed to isolate CD4+ T cells expressing abortive or elongated HIV-1 transcripts from five ART-na\u00efve PWH for transcriptomic analysis by 3\u2019 RNA sequencing. Supervised cluster analysis identified several differentially expressed mitochondrial genes in infected CD4+ T cells with abortive HIV-1 transcripts compared to cells containing elongated HIV-1 transcripts. Notably, enhancing mitochondrial function induced HIV-1 transcription in PBMC from PWH. Our data strongly suggests that cellular metabolism is involved in maintaining HIV-1 latency and show that improving mitochondrial functions induces HIV-1 transcriptional activity in PWH. These findings underline the relevance of metabolic regulation in HIV-1 infection, and support the development of strategies modulating immunometabolism to target viral latency.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012822","type":"journal-article","created":{"date-parts":[[2025,1,10]],"date-time":"2025-01-10T19:39:02Z","timestamp":1736537942000},"page":"e1012822","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":2,"title":["Transcriptomic HIV-1 reservoir profiling reveals a role for mitochondrial functionality in HIV-1 latency"],"prefix":"10.1371","volume":"21","author":[{"given":"Shirley","family":"Man","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jade","family":"Jansen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefanie","family":"Kroeze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teunis B. H.","family":"Geijtenbeek","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9429-7754","authenticated-orcid":true,"given":"Neeltje A.","family":"Kootstra","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2025,1,10]]},"reference":[{"issue":"17","key":"ppat.1012822.ref001","doi-asserted-by":"crossref","DOI":"10.1172\/JCI171554","article-title":"The latent reservoir of inducible, infectious HIV-1 does not decrease despite decades of antiretroviral therapy","volume":"133","author":"NF McMyn","year":"2023","journal-title":"J Clin Invest"},{"issue":"3","key":"ppat.1012822.ref002","doi-asserted-by":"crossref","first-page":"813","DOI":"10.1016\/j.celrep.2017.09.081","article-title":"Identification of Genetically Intact HIV-1 Proviruses in Specific CD4(+) T Cells from Effectively Treated 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