{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T23:48:14Z","timestamp":1792540094987,"version":"4.5.0"},"update-to":[{"DOI":"10.1371\/journal.ppat.1012446","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000}}],"reference-count":36,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T00:00:00Z","timestamp":1723075200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1183032"],"award-info":[{"award-number":["1183032"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1149990"],"award-info":[{"award-number":["1149990"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000026","name":"National Institute on Drug Abuse","doi-asserted-by":"publisher","award":["R21DA055489"],"award-info":[{"award-number":["R21DA055489"]}],"id":[{"id":"10.13039\/100000026","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Locarnini Fellowship in Virology at the Doherty Institute"}],"content-domain":{"domain":["www.plospathogens.org"],"crossmark-restriction":false},"short-container-title":["PLoS Pathog"],"abstract":"<jats:p>HIV persistence in the brain is a barrier to cure, and potentially contributes to HIV-associated neurocognitive disorders. Whether HIV transcription persists in the brain despite viral suppression with antiretroviral therapy (ART) and is subject to the same blocks to transcription seen in other tissues and blood, is unclear. Here, we quantified the level of HIV transcripts in frontal cortex tissue from virally suppressed or non-virally suppressed people with HIV (PWH).<\/jats:p>\n                  <jats:p>HIV transcriptional profiling of frontal cortex brain tissue (and PBMCs where available) from virally suppressed (n = 11) and non-virally suppressed PWH (n = 13) was performed using digital polymerase chain reaction assays (dPCR). CD68+ myeloid cells or CD3+ T cells expressing HIV p24 protein present in frontal cortex tissue was detected using multiplex immunofluorescence imaging.<\/jats:p>\n                  <jats:p>Frontal cortex brain tissue from PWH had HIV TAR (n = 23\/24) and Long-LTR (n = 20\/24) transcripts. Completion of HIV transcription was evident in brain tissue from 12\/13 non-virally suppressed PWH and from 5\/11 virally suppressed PWH, with HIV p24+CD68+ cells detected in these individuals. While a block to proximal elongation was present in frontal cortex tissue from both PWH groups, this block was more extensive in virally suppressed PWH.<\/jats:p>\n                  <jats:p>These findings suggest that the brain is a transcriptionally active HIV reservoir in a subset of virally suppressed PWH.<\/jats:p>","DOI":"10.1371\/journal.ppat.1012446","type":"journal-article","created":{"date-parts":[[2024,8,8]],"date-time":"2024-08-08T13:52:45Z","timestamp":1723125165000},"page":"e1012446","update-policy":"https:\/\/doi.org\/10.1371\/journal.ppat.corrections_policy","source":"Crossref","is-referenced-by-count":37,"title":["HIV transcription persists in the brain of virally suppressed people with HIV"],"prefix":"10.1371","volume":"20","author":[{"given":"Janna","family":"Jamal Eddine","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas A.","family":"Angelovich","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingling","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah J.","family":"Byrnes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolin","family":"Tumpach","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadia","family":"Saraya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily","family":"Chalmers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rory A.","family":"Shepherd","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abigail","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Marinis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul R.","family":"Gorry","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacob D.","family":"Estes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce J.","family":"Brew","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon R.","family":"Lewin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sushama","family":"Telwatte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Roche","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5510-7954","authenticated-orcid":true,"given":"Melissa J.","family":"Churchill","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2024,8,8]]},"reference":[{"key":"ppat.1012446.ref001","doi-asserted-by":"crossref","first-page":"1271","DOI":"10.1038\/nm.4411","article-title":"Defining total-body AIDS-virus burden with implications for curative strategies","volume":"23","author":"JD Estes","year":"2017","journal-title":"Nat 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Churchill","year":"2006","journal-title":"J Neurovirol"},{"issue":"1","key":"ppat.1012446.ref005","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1007\/s11481-018-9809-2","article-title":"Macrophages but not Astrocytes Harbor HIV DNA in the Brains of HIV-1-Infected Aviremic Individuals on Suppressive Antiretroviral Therapy","volume":"14","author":"A Ko","year":"2019","journal-title":"J Neuroimmune Pharmacol"},{"issue":"4","key":"ppat.1012446.ref006","doi-asserted-by":"crossref","first-page":"1623","DOI":"10.1016\/j.ajpath.2011.06.039","article-title":"Brain cell reservoirs of latent virus in presymptomatic HIV-infected individuals","volume":"179","author":"KA Thompson","year":"2011","journal-title":"Am J Pathol"},{"issue":"3","key":"ppat.1012446.ref007","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1093\/brain\/awy339","article-title":"Blood\u2013brain barrier pericytes as a target for HIV-1 infection","volume":"142","author":"HJ Cho","year":"2019","journal-title":"Brain"},{"issue":"4","key":"ppat.1012446.ref008","doi-asserted-by":"crossref","first-page":"532","DOI":"10.1002\/ana.26456","article-title":"Intact HIV Proviruses Persist in the Brain Despite Viral Suppression with ART","volume":"92","author":"CR Cochrane","year":"2022","journal-title":"Ann Neurol"},{"issue":"6","key":"ppat.1012446.ref009","doi-asserted-by":"crossref","first-page":"e0054323","DOI":"10.1128\/jvi.00543-23","article-title":"Evaluation of Archival HIV DNA in Brain and Lymphoid Tissues","volume":"97","author":"MF Oliveira","year":"2023","journal-title":"J Virol"},{"issue":"4","key":"ppat.1012446.ref010","doi-asserted-by":"crossref","first-page":"798","DOI":"10.1002\/ana.26750","article-title":"Regional Analysis of Intact and Defective HIV Proviruses in the Brain of Viremic and Virally Suppressed People with HIV","volume":"94","author":"TA Angelovich","year":"2023","journal-title":"Ann Neurol"},{"issue":"4","key":"ppat.1012446.ref011","doi-asserted-by":"crossref","first-page":"1009","DOI":"10.3390\/v15041009","article-title":"Intact Proviral DNA Analysis of the Brain Viral Reservoir and Relationship to Neuroinflammation in People with HIV on Suppressive Antiretroviral Therapy","volume":"15","author":"D Gabuzda","year":"2023","journal-title":"Viruses"},{"issue":"12","key":"ppat.1012446.ref012","doi-asserted-by":"crossref","first-page":"e167417","DOI":"10.1172\/JCI167417","article-title":"Brain microglia serve as a persistent HIV reservoir despite durable antiretroviral therapy","volume":"133","author":"Y Tang","year":"2023","journal-title":"J Clin Invest"},{"issue":"7","key":"ppat.1012446.ref013","doi-asserted-by":"crossref","first-page":"e25738","DOI":"10.1002\/jia2.25738","article-title":"Tissue-specific differences in HIV DNA levels and mechanisms that govern HIV transcription in blood, gut, genital tract and liver in ART-treated women","volume":"24","author":"S 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Guhaniyogi","year":"2001","journal-title":"Gene"},{"issue":"5","key":"ppat.1012446.ref032","doi-asserted-by":"crossref","first-page":"530","DOI":"10.1097\/QAI.0000000000002287","article-title":"Antiretroviral Therapy Concentrations Differ in Gut vs. Lymph Node Tissues and Are Associated With HIV Viral Transcription by a Novel RT-ddPCR Assay","volume":"83","author":"SA Lee","year":"2020","journal-title":"J Acquir Immune Defic Syndr"},{"issue":"6","key":"ppat.1012446.ref033","doi-asserted-by":"crossref","first-page":"611","DOI":"10.3390\/pathogens11060611","article-title":"HIV Latency in Myeloid Cells: Challenges for a Cure","volume":"11","author":"A Chitrakar","year":"2022","journal-title":"Pathogens"},{"key":"ppat.1012446.ref034","doi-asserted-by":"crossref","first-page":"103241","DOI":"10.1016\/j.ebiom.2021.103241","article-title":"Multiply spliced HIV RNA is a predictive measure of virus production ex vivo and in vivo following reversal of HIV latency","volume":"65","author":"JM Zerbato","year":"2021","journal-title":"EBioMedicine"},{"issue":"4","key":"ppat.1012446.ref035","doi-asserted-by":"crossref","first-page":"326","DOI":"10.1046\/j.0305-1846.2001.00334.x","article-title":"The National NeuroAIDS Tissue Consortium: a new paradigm in brain banking with an emphasis on infectious disease","volume":"27","author":"S Morgello","year":"2001","journal-title":"Neuropathol Appl Neurobiol"},{"key":"ppat.1012446.ref036","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jviromet.2016.12.017","article-title":"Assays for precise quantification of total (including short) and elongated HIV-1 transcripts","volume":"242","author":"P Kaiser","year":"2017","journal-title":"J Virological Methods"}],"updated-by":[{"DOI":"10.1371\/journal.ppat.1012446","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2024,8,20]],"date-time":"2024-08-20T00:00:00Z","timestamp":1724112000000}}],"container-title":["PLOS 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