{"doi":"10.1101/2024.02.15.580166","title":"Metformin Enhances Antibody-Mediated Recognition of HIV-Infected CD4+ T-Cells by Decreasing Viral Release","abstract":"The mechanistic target of rapamycin (mTOR) positively regulates multiple steps of the HIV-1 replication cycle. We previously reported that a 12-weeks supplementation of antiretroviral therapy (ART) with metformin, an indirect mTOR inhibitor used in type-2 diabetes treatment, reduced mTOR activation and HIV transcription in colon-infiltrating CD4+ T-cells, together with systemic inflammation in nondiabetic people with HIV-1 (PWH). Herein, we investigated the antiviral mechanisms of metformin. In a viral outgrowth assay performed with CD4+ T-cells from ART-treated PWH, and upon infection in vitro with replication-competent and VSV-G-pseudotyped HIV-1, metformin decreased virion release, but increased the frequency of productively infected CD4lowHIV-p24+ T-cells. These observations coincided with increased BST2/Tetherin (HIV release inhibitor) and Bcl-2 (pro-survival factor) expression, and improved recognition of productively infected T-cells by HIV-1 Envelope antibodies. Thus, metformin exerts pleiotropic effects on post-transcription/translation steps of the HIV-1 replication cycle and may be used to accelerate viral reservoir decay in ART-treated PWH.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2024,"id":490069,"datarank":0.10397207708399181,"base_score":0.6931471805599453,"endowment":0.6931471805599453,"self_citation_contribution":0.10397207708399181,"citation_network_contribution":0.0,"self_endowment_contribution":0.10397207708399181,"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":0.9548,"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":241566,"name":"Jonathan Richard","orcid":"0000-0002-9015-9589","position":1,"is_corresponding":false},{"id":737994,"name":"Laurence Raymond Marchand","orcid":null,"position":2,"is_corresponding":false},{"id":870125,"name":"Delphine Planas","orcid":"0000-0002-2509-9954","position":3,"is_corresponding":false},{"id":233493,"name":"Jean‐Pierre Routy","orcid":"0000-0001-9897-7589","position":4,"is_corresponding":false},{"id":235294,"name":"Nicolas Chomont","orcid":"0000-0001-9747-5018","position":5,"is_corresponding":false},{"id":241588,"name":"Andrés Finzi","orcid":"0000-0002-4992-5288","position":6,"is_corresponding":false},{"id":18101,"name":"Petronela Ancuța","orcid":"0000-0003-1922-5640","position":7,"is_corresponding":false},{"id":1120496,"name":"Augustine Fert","orcid":null,"position":0,"is_corresponding":true}],"reference_count":123,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:08:32.775003Z","pmid":"38464135","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":[]}