{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE345nnn/GSE345988/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE345988"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Mitophagy-dependent metabolic checkpoint controls seeding of HIV-1 latent reservoir","description":"Achieving a functional cure for HIV-1 remains a major challenge due to the persistence of highly stable viral latent reservoirs under long-term antiretroviral therapy (ART), particularly within resting memory CD4+ T cells. Current cure strategies have largely focused on reducing established reservoirs, with limited attention given to early interventions that could prevent reservoir seeding and contribute to post-treatment control. The cellular mechanisms that govern latent reservoir establishment are still not well understood. Here, we identified mitochondrial damage and mitophagy as defining features of effector-to-memory transitioning (EMT) CD4+ T cells, the primary targets for latent infection. Inhibiting mitophagy triggered ferroptosis, thereby impairing memory CD4+ T cell formation. Specifically, CCR5+ EMT CD4+ T cells, which are critical for latent reservoir seeding, displayed elevated mitochondrial damage and relied on mitophagy for survival. Pharmacological blockade of mitophagy selectively prevented the formation of CCR5+ EMT-derived memory CD4+ T cells, reduced latent HIV-1 infection, and significantly delayed viral rebound after ART interruption in an HIV-1-infected humanized mouse model. Together, these findings reveal a novel strategy to block latent reservoir seeding by inducing ferroptosis in CCR5+ EMT CD4+ T cells, offering a promising avenue for achieving sustained viral remission and advancing efforts toward a functional cure for AIDS.","dates":{"publication":"2026/10/01"},"accession":"GSE345988","cross_references":{"GSM":["GSM10020973","GSM10020972","GSM10020971","GSM10020970","GSM10020969","GSM10020974"],"GPL":["16791"],"GSE":["345988"],"taxon":["Homo sapiens"]}}