{"doi":"10.1016/j.cels.2025.101402","title":"Mild HIV-specific selective forces overlaying natural CD4+ T cell dynamics explain the clonality and decay dynamics of HIV reservoir cells","abstract":"To determine whether HIV persistence arises from the natural dynamics of memory (m)CD4+ T cells, we compare clonal dynamics of HIV proviruses and mCD4+ T cells from the same people living with HIV (PWH) on antiretroviral therapy and from matched HIV-seronegative people (N = 51). HIV proviruses are more clonal than mCD4+ T cells but similarly clonal to antigen-specific cells. Increasing reservoir clonality over time and differential decay of intact and defective proviruses are not explained by mCD4+ T cell kinetics alone. We develop and validate a stochastic model trained on 10 quantitative data metrics, which shows that negative selection against HIV-infected cells is necessary to explain all metrics. We estimate the strength of negative selection, finding that death of cells harboring intact and defective proviruses is infrequently (∼6% and ∼2% on average) due to HIV-specific factors. Thus, our data indicate that HIV persistence is mostly, but not entirely, driven by natural mCD4+ kinetics.","journal":"Cell Systems","year":2025,"id":534811,"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":2,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9584,"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":287410,"name":"Danielle Rigau","orcid":null,"position":1,"is_corresponding":false},{"id":1330847,"name":"Arianna Romero","orcid":null,"position":2,"is_corresponding":false},{"id":653777,"name":"Hao Zhang","orcid":"0000-0002-1304-5895","position":3,"is_corresponding":false},{"id":251144,"name":"Francesco R. Simonetti","orcid":"0000-0002-4165-660X","position":4,"is_corresponding":false},{"id":228709,"name":"Joseph Varriale","orcid":"0000-0002-9663-3325","position":5,"is_corresponding":false},{"id":71690,"name":"Rebecca Hoh","orcid":"0000-0001-5112-4220","position":6,"is_corresponding":false},{"id":1330463,"name":"Li Zhang","orcid":"0000-0002-7100-7168","position":7,"is_corresponding":false},{"id":62880,"name":"Kellie N. Smith","orcid":"0000-0002-6295-8930","position":8,"is_corresponding":false},{"id":251284,"name":"Luis J. Montaner","orcid":"0000-0001-5799-6759","position":9,"is_corresponding":false},{"id":259565,"name":"Leah H. Rubin","orcid":"0000-0003-2749-6328","position":10,"is_corresponding":false},{"id":240246,"name":"Stephen J. Gange","orcid":"0000-0001-7842-512X","position":11,"is_corresponding":false},{"id":71692,"name":"Nadia R. Roan","orcid":"0000-0002-5464-1976","position":12,"is_corresponding":false},{"id":150354,"name":"Phyllis C. Tien","orcid":null,"position":13,"is_corresponding":false},{"id":40987,"name":"Joseph B. Margolick","orcid":"0000-0002-4398-8851","position":14,"is_corresponding":false},{"id":228705,"name":"Michael J. Peluso","orcid":"0000-0003-0585-6230","position":15,"is_corresponding":false},{"id":71691,"name":"Steven G. Deeks","orcid":"0000-0001-6371-747X","position":16,"is_corresponding":false},{"id":246662,"name":"Joshua T. Schiffer","orcid":"0000-0002-2598-1621","position":17,"is_corresponding":false},{"id":228714,"name":"Janet D. Siliciano","orcid":"0000-0001-6712-3775","position":18,"is_corresponding":false},{"id":228713,"name":"Robert F. Siliciano","orcid":"0000-0002-1764-1993","position":19,"is_corresponding":false},{"id":286352,"name":"Annukka A.R. Antar","orcid":"0000-0002-6775-1103","position":20,"is_corresponding":false},{"id":286355,"name":"Daniel B. Reeves","orcid":"0000-0001-5684-9538","position":0,"is_corresponding":true}],"reference_count":101,"raw_metadata":null,"created_at":"2026-07-19T02:51:52.019261Z","pmid":"40987290","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":[]}