{"doi":"10.1371/journal.ppat.1012446","title":"HIV transcription persists in the brain of virally suppressed people with HIV","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>","journal":"PLOS Pathogens","year":2024,"id":611672,"datarank":0.4943755299006494,"base_score":3.295836866004329,"endowment":3.295836866004329,"self_citation_contribution":0.4943755299006494,"citation_network_contribution":0.0,"self_endowment_contribution":0.4943755299006494,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":521058,"name":"Thomas A. 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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>","is_dataset_classified":null,"base_score":3.1780538303479458,"endowment":3.1780538303479458,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"39116185","pmcid":"PMC11335163","openalex_id":"https://openalex.org/W4401416973","authors":[],"funders":[{"funder_name":"National Health and Medical Research Council","grant_id":"1183032","title":null},{"funder_name":"National Health and Medical Research Council","grant_id":"1149990","title":"Addressing the major challenges in HIV vaccine and cure research"},{"funder_name":"National Institute on Drug Abuse","grant_id":"R21DA055489","title":null},{"funder_name":"National Institutes of Health","grant_id":"1R21DA055489-01","title":"Characterization of the intact and defective HIV reservoirs in myeloid cells in the brain"},{"funder_name":"Fundação para a Ciência e a Tecnologia, I.P.","grant_id":"PTDC/CCI-BIO/29266/2017","title":"Deep Drug Discovery and Deployment"},{"funder_name":"Locarnini Fellowship in Virology at the Doherty Institute","grant_id":"","title":null}],"total_grants":6,"fwci":5.3599,"citation_percentile":0.96266667,"influential_citations":0,"citation_trend":[{"year":2024,"count":3},{"year":2025,"count":8},{"year":2026,"count":12}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"https://doi.org/10.1371/journal.ppat.1012446","host_type":"journal"},{"url":"https://doi.org/10.1371/journal.ppat.1012446","host_type":"publisher"},{"url":"https://dx.plos.org/10.1371/journal.ppat.1012446","host_type":"publisher"},{"url":"https://pubmed.ncbi.nlm.nih.gov/39116185","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/11335163","host_type":"repository"},{"url":"https://researchonline.nd.edu.au/med_article/1858","host_type":"repository"},{"url":"https://doaj.org/article/a288983a01634826840f2cf6e23b2dd3","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC11335163/pdf/ppat.1012446.pdf","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC11335163","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC11335163?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1371/journal.ppat.1012446","host_type":""}],"fields_of_study":["HIV Research and Treatment","HIV/AIDS Research and Interventions","HIV-related health complications and treatments"],"mesh_terms":["Adult","Brain","Female","Frontal Lobe","Humans","Male","Middle Aged","Transcription, Genetic","HIV-1","HIV Infections"],"keywords":["CD68","Virology","Medicine","Cortex (anatomy)","Reverse transcriptase","Biology","Immunology","RNA","Neuroscience","Immunohistochemistry","Gene","Male","Adult","Transcription, Genetic","QH301-705.5","Brain","HIV Infections","RC581-607","Middle Aged","Frontal Lobe","616","Medicine and Health Sciences","HIV-1","Humans","Female","Immunologic diseases. 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