{"doi":"10.1093/jimmun/vkaf283.892","title":"Immunometabolic reprogramming by caloric restriction leads to protection from SIV in rhesus macaques 3052","abstract":"Abstract Description Nutrient metabolism influences HIV-1 replication, immunity, and chronic inflammation, yet it is challenging to target therapeutically. We hypothesized that modulating metabolism via caloric restriction (CR), a safe, anti-aging modality with anti-inflammatory effects could improve SIV disease outcome in rhesus macaques (RMs). Healthy, non-obese, Indian RMs (n = 6) were restricted to 30% fewer daily calories than their ad-libitum (AL) intake. After 3 months of CR, they were infected with SIVmac239, left untreated for 28 days, and then given ART for 11 months while maintaining CR. They were compared to age-, gender-, and weight-matched AL-fed RMs (n = 11). CR led to an approximately 1 log reduction in acute-phase viremia compared to the AL cohort, along with significantly greater memory CD8 T cell proliferative response at prominent tissue sites of SIV replication. Plasma metabolomics showed that CR induced a predominant glycolytic signature and 3 metabolites: spermidine, glucose-6-phosphate, and ADP strongly predicted lower plasma SIV AUC. Ex vivo glycolytic flux and mTORC1 activity were also higher in PBMCs and memory CD8 T cells at acute SIV, respectively. 11 months post-ART, CR cohort exhibited reduced levels of HLA-DR+ CD4 and CD8 memory T cells in the colon and lower plasma levels of the gut permeability marker sCD14. Improved gut health in CR was associated with elevated TCA-cycle intermediates. Thus, the data shows that CR has a profoundly positive impact on SIV pathogenesis. Funding Sources NIH R01 AI67644-01A1; NIH R21 AI74901-01; NIH R21 OD031229. Topic Categories Viral Immunology (VIR)","journal":"The Journal of Immunology","year":2025,"id":582666,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9587,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1177669,"name":"Chrysostomos Perdios","orcid":"0000-0001-6000-6373","position":1,"is_corresponding":false},{"id":1495040,"name":"Anna T. Brown","orcid":null,"position":2,"is_corresponding":false},{"id":676371,"name":"Celeste Coleman","orcid":null,"position":3,"is_corresponding":false},{"id":259614,"name":"Carolina Allers","orcid":"0000-0001-8576-770X","position":4,"is_corresponding":false},{"id":472898,"name":"Matilda J. Moström","orcid":"0000-0001-7261-6638","position":5,"is_corresponding":false},{"id":1495041,"name":"Adam M. Myers","orcid":null,"position":6,"is_corresponding":false},{"id":1495042,"name":"Lara Doyle-Myers","orcid":null,"position":7,"is_corresponding":false},{"id":258547,"name":"Ricki J. Colman","orcid":"0000-0001-9706-0525","position":8,"is_corresponding":false},{"id":1341175,"name":"Pratik Khare","orcid":"0000-0002-1633-8765","position":9,"is_corresponding":false},{"id":232227,"name":"Cissy Zhang","orcid":"0000-0003-0469-2086","position":10,"is_corresponding":false},{"id":259605,"name":"Robert V. Blair","orcid":"0000-0001-9616-9414","position":11,"is_corresponding":false},{"id":1006957,"name":"Ahmad Saied","orcid":"0000-0002-3944-7112","position":12,"is_corresponding":false},{"id":232235,"name":"Anne Le","orcid":"0000-0002-2958-8149","position":13,"is_corresponding":false},{"id":589834,"name":"Clovis S. Palmer","orcid":"0000-0001-9822-4181","position":14,"is_corresponding":false},{"id":293286,"name":"Joseph C. Mudd","orcid":null,"position":15,"is_corresponding":false},{"id":1495039,"name":"Naveen Suresh Babu","orcid":null,"position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:59.653747Z","pmid":null,"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":[]}