{"doi":"10.1093/pnasnexus/pgac064","title":"HIV-1 mutants that escape the cytotoxic T-lymphocytes are defective in viral DNA integration","abstract":"HIV-1 replication is durably controlled without antiretroviral therapy (ART) in certain infected individuals called elite controllers (ECs). These individuals express specific human leukocyte antigens (HLA) that tag HIV-infected cells for elimination by presenting viral epitopes to CD8+ cytotoxic T-lymphocytes (CTL). In HIV-infected individuals expressing HLA-B27, CTLs primarily target the viral capsid protein (CA)-derived KK10 epitope. While selection of CA mutation R264K helps HIV-1 escape this potent CTL response, the accompanying fitness cost severely diminishes virus infectivity. Interestingly, selection of a compensatory CA mutation S173A restores HIV-1 replication. However, the molecular mechanism(s) underlying HIV-1 escape from this ART-free virus control by CTLs is not fully understood. Here, we report that the R264K mutation-associated infectivity defect arises primarily from impaired HIV-1 DNA integration, which is restored by the S173A mutation. Unexpectedly, the integration defect of the R264K variant was also restored upon depletion of the host cyclophilin A. These findings reveal a nuclear crosstalk between CA and HIV-1 integration as well as identify a previously unknown role of cyclophilin A in viral DNA integration. Finally, our study identifies a novel immune escape mechanism of an HIV-1 variant escaping a CA-directed CTL response.","journal":"PNAS Nexus","year":2022,"id":262102,"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":14,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9539,"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":722445,"name":"Benem-Orom Davids","orcid":null,"position":1,"is_corresponding":false},{"id":829894,"name":"Alex Bryer","orcid":null,"position":2,"is_corresponding":false},{"id":307285,"name":"Chaoyi Xu","orcid":"0000-0002-9870-4297","position":3,"is_corresponding":false},{"id":304674,"name":"Santosh Thapa","orcid":"0000-0002-4534-1349","position":4,"is_corresponding":false},{"id":298945,"name":"Jiong Shi","orcid":"0000-0001-7548-7616","position":5,"is_corresponding":false},{"id":307290,"name":"Christopher Aiken","orcid":"0000-0002-2476-4078","position":6,"is_corresponding":false},{"id":374804,"name":"Jui Pandhare","orcid":"0000-0002-0356-064X","position":7,"is_corresponding":false},{"id":298286,"name":"Juan R. Perilla","orcid":"0000-0003-1171-6816","position":8,"is_corresponding":false},{"id":374805,"name":"Chandravanu Dash","orcid":"0000-0003-4466-8355","position":9,"is_corresponding":false},{"id":374800,"name":"Muthukumar Balasubramaniam","orcid":"0000-0002-0979-6186","position":0,"is_corresponding":true}],"reference_count":100,"raw_metadata":null,"created_at":"2026-07-19T00:26:20.717229Z","pmid":"35719891","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":[]}