{"doi":"10.1016/j.immuni.2024.11.002","title":"Cognate antigen engagement induces HIV-1 expression in latently infected CD4+ T cells from people on long-term antiretroviral therapy","abstract":"Despite antiretroviral therapy (ART), HIV-1 persists in latently infected CD4 + T cells, preventing a cure. Antigens drive the proliferation of infected cells, precluding latent reservoir decay. However, the relationship between antigen recognition and HIV-1 gene expression is poorly understood because most studies of latency reversal use agents that induce non-specific global T cell activation. Here, we isolated rare CD4 + T cells responding to cytomegalovirus (CMV) or HIV-1 Gag antigens from people living with HIV-1 on long-term ART and assessed T cell activation and HIV-1 RNA expression upon coculture with autologous dendritic cells (DCs) presenting cognate antigens. Presentation of cognate antigens ex vivo induced broad T cell activation (median 42-fold increase in CD154 + CD69 + cells) and significantly increased HIV-1 transcription (median 4-fold), mostly through the induction of rare cells with higher viral expression. Thus, despite low proviral inducibility, antigen recognition can promote HIV-1 expression, potentially contributing to spontaneous reservoir activity and viral rebound upon ART interruption.","journal":"Immunity","year":2024,"id":435908,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":12,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9524,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":370713,"name":"Filippo Dragoni","orcid":"0000-0002-8148-9914","position":1,"is_corresponding":false},{"id":876484,"name":"Nathan L. Board","orcid":"0000-0002-5208-9970","position":2,"is_corresponding":false},{"id":827792,"name":"Fengting Wu","orcid":"0000-0001-6320-8288","position":3,"is_corresponding":false},{"id":239683,"name":"Jun Lai","orcid":"0009-0008-6435-2888","position":4,"is_corresponding":false},{"id":653777,"name":"Hao Zhang","orcid":"0000-0002-1304-5895","position":5,"is_corresponding":false},{"id":29183,"name":"James R. White","orcid":"0000-0002-7535-9179","position":6,"is_corresponding":false},{"id":71690,"name":"Rebecca Hoh","orcid":"0000-0001-5112-4220","position":7,"is_corresponding":false},{"id":296791,"name":"Kenneth Lynn","orcid":null,"position":8,"is_corresponding":false},{"id":58750,"name":"Pablo Tebas","orcid":"0000-0001-5345-7942","position":9,"is_corresponding":false},{"id":263031,"name":"Karam Mounzer","orcid":"0000-0001-8537-7103","position":10,"is_corresponding":false},{"id":71691,"name":"Steven G. Deeks","orcid":"0000-0001-6371-747X","position":11,"is_corresponding":false},{"id":251284,"name":"Luis J. Montaner","orcid":"0000-0001-5799-6759","position":12,"is_corresponding":false},{"id":228714,"name":"Janet D. Siliciano","orcid":"0000-0001-6712-3775","position":13,"is_corresponding":false},{"id":228713,"name":"Robert F. Siliciano","orcid":"0000-0002-1764-1993","position":14,"is_corresponding":false},{"id":251144,"name":"Francesco R. Simonetti","orcid":"0000-0002-4165-660X","position":15,"is_corresponding":false},{"id":1018060,"name":"Milica Moskovljevic","orcid":"0000-0003-0436-6854","position":0,"is_corresponding":true}],"reference_count":107,"raw_metadata":null,"created_at":"2026-07-19T02:00:08.103086Z","pmid":"39612916","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}