{"doi":"10.1084/jem.20211427","title":"Integration features of intact latent HIV-1 in CD4+ T cell clones contribute to viral persistence","abstract":"Latent intact HIV-1 proviruses persist in a small subset of long-lived CD4+ T cells that can undergo clonal expansion in vivo. Expanded clones of CD4+ T cells dominate latent reservoirs in individuals on long-term antiretroviral therapy (ART) and represent a major barrier to HIV-1 cure. To determine how integration landscape might contribute to latency, we analyzed integration sites of near full length HIV-1 genomes from individuals on long-term ART, focusing on individuals whose reservoirs are highly clonal. We find that intact proviruses in expanded CD4+ T cell clones are preferentially integrated within Krüppel-associated box (KRAB) domain-containing zinc finger (ZNF) genes. ZNF genes are associated with heterochromatin in memory CD4+ T cells; nevertheless, they are expressed in these cells under steady-state conditions. In contrast to genes carrying unique integrations, ZNF genes carrying clonal intact integrations are down-regulated upon cellular activation. Together, the data suggest selected genomic sites, including ZNF genes, can be especially permissive for maintaining HIV-1 latency during memory CD4+ T cell expansion.","journal":"The Journal of Experimental Medicine","year":2021,"id":151814,"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":80,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9569,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2021-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":104721,"name":"Víctor Ramos","orcid":"0000-0001-7353-3420","position":1,"is_corresponding":false},{"id":104712,"name":"Thiago Y. Oliveira","orcid":"0000-0002-2654-0879","position":2,"is_corresponding":false},{"id":104704,"name":"Christian Gaebler","orcid":"0000-0001-7295-8128","position":3,"is_corresponding":false},{"id":254283,"name":"Mila Janković","orcid":"0000-0001-9696-5234","position":4,"is_corresponding":false},{"id":104187,"name":"Michel C. Nussenzweig","orcid":"0000-0003-0592-8564","position":5,"is_corresponding":false},{"id":235293,"name":"Lillian B. Cohn","orcid":"0000-0002-3485-8692","position":6,"is_corresponding":false},{"id":644989,"name":"Amy S. Huang","orcid":"0000-0002-5303-2191","position":0,"is_corresponding":true}],"reference_count":67,"raw_metadata":null,"created_at":"2026-07-18T23:43:16.823357Z","pmid":"34636876","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":[]}