{"doi":"10.26508/lsa.202402653","title":"Transcriptional and methylation outcomes of didehydro-cortistatin A use in HIV-1–infected CD4<sup>+</sup>T cells","abstract":"Ongoing viral transcription from the reservoir of HIV-1 infected long-lived memory CD4 + T cells presents a barrier to cure and associates with poorer health outcomes for people living with HIV, including chronic immune activation and inflammation. We previously reported that didehydro-cortistatin A (dCA), an HIV-1 Tat inhibitor, blocks HIV-1 transcription. Here, we examine the impact of dCA on host immune CD4 + T-cell transcriptional and epigenetic states. We performed a comprehensive analysis of genome-wide transcriptomic and DNA methylation profiles upon long-term dCA treatment of primary human memory CD4 + T cells. dCA prompted specific transcriptional and DNA methylation changes in cell cycle, histone, interferon-response, and T-cell lineage transcription factor genes, through inhibition of both HIV-1 and Mediator kinases. These alterations establish a tolerogenic Treg/Th2 phenotype, reducing viral gene expression and mitigating inflammation in primary CD4 + T cells during HIV-1 infection. In addition, dCA suppresses the expression of lineage-defining transcription factors for Th17 and Th1 cells, critical HIV-1 targets, and reservoirs. dCA’s benefits thus extend beyond viral transcription inhibition, modulating the immune cell landscape to limit HIV-1 acquisition and inflammatory environment linked to HIV infection.","journal":"Life Science Alliance","year":2024,"id":468739,"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":3,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.948,"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":69463,"name":"Michael J. Corley","orcid":"0000-0001-8957-7153","position":1,"is_corresponding":false},{"id":846267,"name":"Andrew McAuley","orcid":"0000-0002-6047-2400","position":2,"is_corresponding":false},{"id":69482,"name":"Alina P.S. Pang","orcid":"0000-0001-6677-7355","position":3,"is_corresponding":false},{"id":817333,"name":"Thomas Venables","orcid":"0000-0002-2299-0389","position":4,"is_corresponding":false},{"id":69472,"name":"Lishomwa C. Ndhlovu","orcid":"0000-0001-5427-4187","position":5,"is_corresponding":false},{"id":259945,"name":"Matthew E. Pipkin","orcid":"0000-0002-9688-0190","position":6,"is_corresponding":false},{"id":291490,"name":"Susana T. Valente","orcid":"0000-0002-7854-7554","position":7,"is_corresponding":false},{"id":1302228,"name":"Luisa P Mori","orcid":null,"position":0,"is_corresponding":true}],"reference_count":49,"raw_metadata":null,"created_at":"2026-07-19T02:05:23.500722Z","pmid":"39089880","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":[]}