{"doi":"10.1101/2021.08.29.458043","title":"HIV-1 Mutants that Escape the Cytotoxic T-Lymphocytes are Defective in Viral DNA Integration","abstract":"ABSTRACT HIV-1 replication is durably controlled in certain untreated HIV-1-infected individuals expressing particular human leukocyte antigens (HLA). These HLAs tag infected cells for elimination by presenting specific viral epitopes to CD8+ cytotoxic T-lymphocytes (CTL). In individuals expressing HLA-B27, CTLs primarily target the capsid protein (CA)-derived KK10 epitope. Selection of CA mutation R264K helps HIV-1 escape the CTL response but severely diminishes virus infectivity. Here we report that the R264K mutation-associated infectivity defect arises primarily from impaired viral DNA integration. Strikingly, selection of the compensatory CA mutation S173A or depletion of host cyclophilin A largely rescues the R264K-associated integration and infectivity defects. Collectively, our study reveals novel mechanistic insights into the fitness defect incurred by an HIV-1 variant escaping a CA-directed CTL response.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2021,"id":226528,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9513,"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":304674,"name":"Santosh Thapa","orcid":"0000-0002-4534-1349","position":1,"is_corresponding":false},{"id":722445,"name":"Benem-Orom Davids","orcid":null,"position":2,"is_corresponding":false},{"id":829894,"name":"Alex Bryer","orcid":null,"position":3,"is_corresponding":false},{"id":307285,"name":"Chaoyi Xu","orcid":"0000-0002-9870-4297","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":163,"raw_metadata":null,"created_at":"2026-07-18T23:54:34.185847Z","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":[]}