{"doi":"10.1172/jci.insight.162290","title":"Blockade of TGF-β signaling reactivates HIV-1/SIV reservoirs and immune responses in vivo","abstract":"TGF-β plays a critical role in maintaining immune cells in a resting state by inhibiting cell activation and proliferation. Resting HIV-1 target cells represent the main cellular reservoir after long-term antiretroviral therapy (ART). We hypothesized that releasing cells from TGF-β-driven signaling would promote latency reversal. To test our hypothesis, we compared HIV-1 latency models with and without TGF-β and a TGF-β type 1 receptor inhibitor, galunisertib. We tested the effect of galunisertib in SIV-infected, ART-treated macaques by monitoring SIV-env expression via PET/CT using the 64Cu-DOTA-F(ab')2 p7D3 probe, along with plasma and tissue viral loads (VLs). Exogenous TGF-β reduced HIV-1 reactivation in U1 and ACH-2 models. Galunisertib increased HIV-1 latency reversal ex vivo and in PBMCs from HIV-1-infected, ART-treated, aviremic donors. In vivo, oral galunisertib promoted increased total standardized uptake values in PET/CT images in gut and lymph nodes of 5 out of 7 aviremic, long-term ART-treated, SIV-infected macaques. This increase correlated with an increase in SIV RNA in the gut. Two of the 7 animals also exhibited increases in plasma VLs. Higher anti-SIV T cell responses and antibody titers were detected after galunisertib treatment. In summary, our data suggest that blocking TGF-β signaling simultaneously increases retroviral reactivation events and enhances anti-SIV immune responses.","journal":"JCI Insight","year":2022,"id":244928,"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":26,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9551,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":586949,"name":"Yanique Thomas","orcid":"0000-0003-0602-7493","position":1,"is_corresponding":false},{"id":586945,"name":"Mariluz Araínga","orcid":"0000-0002-4533-5854","position":2,"is_corresponding":false},{"id":878855,"name":"Crystal Carter","orcid":"0000-0001-8929-3839","position":3,"is_corresponding":false},{"id":618115,"name":"Lisa Shirreff","orcid":"0000-0002-8403-451X","position":4,"is_corresponding":false},{"id":748214,"name":"Muhammad Arif","orcid":"0000-0001-7129-3312","position":5,"is_corresponding":false},{"id":879313,"name":"Juan M. Avita","orcid":null,"position":6,"is_corresponding":false},{"id":443304,"name":"Ines Frank","orcid":"0000-0001-9345-9942","position":7,"is_corresponding":false},{"id":586943,"name":"Michael D. McRaven","orcid":"0000-0002-3098-1394","position":8,"is_corresponding":false},{"id":879314,"name":"Christopher T. Thuruthiyil","orcid":null,"position":9,"is_corresponding":false},{"id":878856,"name":"Veli B. Heybeli","orcid":"0000-0001-5925-1056","position":10,"is_corresponding":false},{"id":586948,"name":"Meegan R. Anderson","orcid":"0000-0002-2569-2141","position":11,"is_corresponding":false},{"id":878857,"name":"Benjamin Owen","orcid":"0000-0002-4549-7845","position":12,"is_corresponding":false},{"id":602622,"name":"Arsen Gaisin","orcid":null,"position":13,"is_corresponding":false},{"id":800097,"name":"Deepanwita Bose","orcid":"0000-0003-4164-6556","position":14,"is_corresponding":false},{"id":281228,"name":"Lacy M. Simons","orcid":"0000-0003-4041-6775","position":15,"is_corresponding":false},{"id":36741,"name":"Judd F. Hultquist","orcid":"0000-0001-6424-4280","position":16,"is_corresponding":false},{"id":367028,"name":"James Arthos","orcid":"0000-0002-6767-4267","position":17,"is_corresponding":false},{"id":367029,"name":"Claudia Cicala","orcid":"0000-0002-1181-8997","position":18,"is_corresponding":false},{"id":241760,"name":"Irini Sereti","orcid":"0000-0002-0076-0224","position":19,"is_corresponding":false},{"id":320918,"name":"Philip J. Santangelo","orcid":"0000-0001-7352-0339","position":20,"is_corresponding":false},{"id":283126,"name":"Ramón Lorenzo-Redondo","orcid":"0000-0002-5462-9483","position":21,"is_corresponding":false},{"id":263030,"name":"Thomas J. Hope","orcid":"0000-0001-7183-8319","position":22,"is_corresponding":false},{"id":258352,"name":"François Villinger","orcid":"0000-0002-7790-2008","position":23,"is_corresponding":false},{"id":443305,"name":"Elena Martinelli","orcid":"0000-0002-3416-9627","position":24,"is_corresponding":false},{"id":879312,"name":"Sadia Samer","orcid":null,"position":0,"is_corresponding":true}],"reference_count":82,"raw_metadata":null,"created_at":"2026-07-19T00:23:30.364338Z","pmid":"36125890","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":[]}