{"doi":"10.1101/2022.08.03.502655","title":"The Hypoxia-regulated Ectonucleotidase CD73 is a Host Determinant of HIV Latency","abstract":"SUMMARY Deciphering the mechanisms underlying viral persistence is critical to achieving a cure for HIV infection. We implemented a systems approach to discover molecular signatures of HIV latently-infected CD4+ T cells, identifying the immunosuppressive, adenosine-producing ectonucleotidase CD73 as a key surface marker of latent cells. Hypoxic conditioning, reflecting the lymphoid tissue microenvironment, increased the frequency of CD73+ CD4+ T cells and promoted HIV latency. Transcriptomic profiles of CD73+ CD4+ T cells favored viral quiescence, immune evasion, and cell survival. CD73+ CD4+ T cells were capable of harboring a functional HIV reservoir and reinitiating productive infection ex vivo . CD73 or adenosine receptor blockade facilitated latent HIV reactivation in vitro , mechanistically linking adenosine signaling to viral quiescence. Finally, tissue imaging of lymph nodes from HIV-infected individuals on antiretroviral therapy revealed spatial association between CD73 expression and HIV persistence in vivo . Our findings warrant development of HIV cure strategies targeting the hypoxia-CD73-adenosine axis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":303980,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9574,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":290820,"name":"Kyle A. Raymond","orcid":"0000-0001-8670-2852","position":1,"is_corresponding":false},{"id":537094,"name":"Mohamed S. Bouzidi","orcid":null,"position":2,"is_corresponding":false},{"id":248465,"name":"Tongcui Ma","orcid":null,"position":3,"is_corresponding":false},{"id":683198,"name":"Silvana Valdebenito","orcid":"0000-0002-6318-632X","position":4,"is_corresponding":false},{"id":683207,"name":"Eliseo A. Eugenín","orcid":"0000-0002-2925-4720","position":5,"is_corresponding":false},{"id":71692,"name":"Nadia R. Roan","orcid":"0000-0002-5464-1976","position":6,"is_corresponding":false},{"id":71691,"name":"Steven G. Deeks","orcid":"0000-0001-6371-747X","position":7,"is_corresponding":false},{"id":996400,"name":"Sandra Winning","orcid":"0000-0002-3788-1054","position":8,"is_corresponding":false},{"id":996401,"name":"Joachim Fandrey","orcid":"0000-0001-9585-0531","position":9,"is_corresponding":false},{"id":355440,"name":"Roland Schwarzer","orcid":"0000-0002-7497-5180","position":10,"is_corresponding":false},{"id":24132,"name":"Satish K. Pillai","orcid":"0000-0001-8770-7014","position":11,"is_corresponding":false},{"id":536381,"name":"Hannah S. Sperber","orcid":"0000-0002-9638-6555","position":0,"is_corresponding":true}],"reference_count":84,"raw_metadata":null,"created_at":"2026-07-19T00:32:28.468841Z","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":[]}