{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE301nnn/GSE301433/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Macaca mulatta"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE301433"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"BCL-2 Inhibition at antiretroviral therapy initiation reduces the intact SIV reservoir in macaques","description":"The anti-apoptotic molecule BCL-2 favors the maintenance of the CD4+ T-cell reservoir during Human immunodeficiency virus (HIV) infection. We investigated directly in-vivo whether BCL-2 inhibition using venetoclax at the initiation of antiretroviral therapy (ART) would reduce the size of the viral reservoir. Twenty-four SIVmac239-infected rhesus macaques (RMs) were initiated on ART at day 14 post-infection (p.i.), alone or in combination with either 10-day treatment with venetoclax or venetoclax plus CD8α depletion, and followed up to day 294 p.i. A rapid, statistically significant, and sustained reduction in the intact SIV reservoir was observed in venetoclax-treated RMs in blood and lymph nodes (LNs). This reduction was driven by reduced survival and depletion of CD4+ T-cell subsets that critically contribute to the reservoir. CD4+ T-cells that persisted after venetoclax treatment exhibited elevated per-cell levels of BCL-2, reduced expression of pro-apoptotic molecules such as PUMA, increased expression of additional anti-apoptotic molecules, including BCL-xL, and a partial reduction in apoptotic sensitivity in ex vivo assays. These findings provide mechanistic insights for the venetoclax-induced pro-cell death changes in CD4+ T-cells, support the rationale for extended venetoclax dosing, and suggest that combining BCL-2 inhibition with agents targeting additional anti-apoptotic molecules can enhance clearance of the viral reservoir in HIV cure strategies.","dates":{"publication":"2026/06/28"},"accession":"GSE301433","cross_references":{"GSM":["GSM9083235","GSM9083224","GSM9083234","GSM9083223","GSM9083237","GSM9083226","GSM9083215","GSM9083236","GSM9083225","GSM9083217","GSM9083228","GSM9083227","GSM9083216","GSM9083219","GSM9083229","GSM9083218","GSM9083220","GSM9083231","GSM9083230","GSM9083233","GSM9083222","GSM9083232","GSM9083221"],"GPL":["27943"],"GSE":["301433"],"taxon":["Macaca mulatta"]}}