{"doi":"10.1101/2022.04.02.486753","title":"Profound phenotypic and epigenetic heterogeneity of the HIV-1 infected CD4+ T cell reservoir","abstract":"Abstract Understanding the complexity of the long-lived HIV reservoir during antiretroviral therapy (ART) remains a major impediment for HIV cure research. To address this, we developed single-cell viral ASAPseq to precisely define the unperturbed peripheral blood HIV-infected memory CD4+ T cell reservoir from antiretroviral treated people living with HIV (ART-PLWH) via the presence of integrated accessible proviral DNA in concert with epigenetic and cell surface protein profiling. We identified profound reservoir heterogeneity within and between ART-PLWH, characterized by novel and known surface markers within total and individual memory CD4+ T cell subsets. We further uncovered novel epigenetic profiles and transcription factor motifs enriched in HIV-infected cells that suggest infected cells with accessible provirus, irrespective of reservoir distribution, are poised for reactivation during ART treatment. Together, our findings reveal the extensive inter- and intrapersonal cellular heterogeneity of the HIV reservoir, and establish an initial multiomic atlas to develop targeted reservoir elimination strategies.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":297907,"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":7,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"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":258048,"name":"Son C. Nguyen","orcid":"0000-0003-2187-1027","position":1,"is_corresponding":false},{"id":849823,"name":"Jayme M.L. Nordin","orcid":"0000-0002-8186-7567","position":2,"is_corresponding":false},{"id":849824,"name":"Jaimy Joy","orcid":"0000-0003-3183-2144","position":3,"is_corresponding":false},{"id":576587,"name":"Felicity Mampe","orcid":null,"position":4,"is_corresponding":false},{"id":58750,"name":"Pablo Tebas","orcid":"0000-0001-5345-7942","position":5,"is_corresponding":false},{"id":251284,"name":"Luis J. Montaner","orcid":"0000-0001-5799-6759","position":6,"is_corresponding":false},{"id":263024,"name":"Katharine J. Bar","orcid":"0000-0002-9773-0071","position":7,"is_corresponding":false},{"id":105479,"name":"Laura A. Vella","orcid":"0000-0002-8917-4845","position":8,"is_corresponding":false},{"id":105481,"name":"Michael R. Betts","orcid":"0000-0002-7690-1484","position":9,"is_corresponding":false},{"id":240546,"name":"Vincent H. Wu","orcid":"0000-0002-8640-6065","position":0,"is_corresponding":true}],"reference_count":83,"raw_metadata":null,"created_at":"2026-07-19T00:31:31.270564Z","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":[]}