{"doi":"10.1101/2023.09.05.556422","title":"TGF-β blockade drives a transitional effector phenotype in T cells reversing SIV latency and decreasing SIV reservoirs <i>in vivo</i>","abstract":"HIV-1 persistence during ART is due to the establishment of long-lived viral reservoirs in resting immune cells. Using an NHP model of barcoded SIVmac239 intravenous infection and therapeutic dosing of the anti-TGFBR1 inhibitor galunisertib (LY2157299), we confirmed the latency reversal properties of in vivo TGF-β blockade, decreased viral reservoirs and stimulated immune responses. Eight SIV-infected macaques on suppressive ART were treated with 4 2-week cycles of galunisertib. ART was discontinued 3 weeks after the last dose, and macaques euthanized 6 weeks after ART-interruption(ATI). One macaque did not rebound, while the remaining rebounded between week 2 and 6 post-ATI. Galunisertib led to viral reactivation as indicated by plasma viral load and immunoPET/CT with the 64Cu-DOTA-F(ab')2-p7D3-probe. Half to 1 Log decrease in cell-associated (CA-)SIV DNA was detected in lymph nodes, gut and PBMC, while intact pro-virus in PBMC decreased by 3-fold. No systemic increase in inflammatory cytokines was observed. High-dimensions cytometry, bulk and single-cell RNAseq revealed a shift toward an effector phenotype in T and NK cells. In summary, we demonstrated that galunisertib, a clinical stage TGFβ inhibitor, reverses SIV latency and decreases SIV reservoirs by driving T cells toward an effector phenotype, enhancing immune responses in vivo in absence of toxicity.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2023,"id":400675,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9466,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":800097,"name":"Deepanwita Bose","orcid":"0000-0003-4164-6556","position":1,"is_corresponding":false},{"id":586945,"name":"Mariluz Araínga","orcid":"0000-0002-4533-5854","position":2,"is_corresponding":false},{"id":847777,"name":"Muhammad R. Haque","orcid":"0000-0002-7487-2667","position":3,"is_corresponding":false},{"id":233485,"name":"Christine M. Fennessey","orcid":"0000-0002-8736-8523","position":4,"is_corresponding":false},{"id":1177441,"name":"Rachel A Caddell","orcid":null,"position":5,"is_corresponding":false},{"id":586949,"name":"Yanique Thomas","orcid":"0000-0003-0602-7493","position":6,"is_corresponding":false},{"id":618116,"name":"Douglas E. Ferrell","orcid":"0000-0001-8871-9690","position":7,"is_corresponding":false},{"id":109399,"name":"Syed Azmal Ali","orcid":"0000-0003-3024-9379","position":8,"is_corresponding":false},{"id":98078,"name":"Emanuelle I. Grody","orcid":"0000-0002-7177-3268","position":9,"is_corresponding":false},{"id":281300,"name":"Yogesh Goyal","orcid":"0000-0003-3502-6465","position":10,"is_corresponding":false},{"id":367029,"name":"Claudia Cicala","orcid":"0000-0002-1181-8997","position":11,"is_corresponding":false},{"id":367028,"name":"James Arthos","orcid":"0000-0002-6767-4267","position":12,"is_corresponding":false},{"id":233486,"name":"Brandon F. Keele","orcid":"0000-0002-2381-1151","position":13,"is_corresponding":false},{"id":259606,"name":"Monica Vaccari","orcid":"0000-0002-4514-2681","position":14,"is_corresponding":false},{"id":283126,"name":"Ramón Lorenzo-Redondo","orcid":"0000-0002-5462-9483","position":15,"is_corresponding":false},{"id":263030,"name":"Thomas J. Hope","orcid":"0000-0001-7183-8319","position":16,"is_corresponding":false},{"id":258352,"name":"François Villinger","orcid":"0000-0002-7790-2008","position":17,"is_corresponding":false},{"id":443305,"name":"Elena Martinelli","orcid":"0000-0002-3416-9627","position":18,"is_corresponding":false},{"id":499231,"name":"Jin-Hee Kim","orcid":"0000-0003-0712-9600","position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T01:20:04.010538Z","pmid":"38014094","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":[]}