{"doi":"10.7554/elife.97348.1.sa1","title":"Reviewer #2 (Public Review): Human immunodeficiency virus-1 induces and targets host genomic R-loops for viral genome integration","abstract":"Although HIV-1 integration sites are considered to favor active transcription units in the human genome, high-resolution analysis of individual HIV-1 integration sites have shown that the virus can integrate in a variety of host genomic locations, including non-genic regions. The invisible infection by HIV-1 integrating into non-genic regions challenging the traditional understanding of HIV-1 integration site selection are rather more problematic as they are selected to preserve in the host genome during prolonged antiretroviral therapies. Here, we showed that HIV-1 targets R-loops, a genomic structure made up of DNA–RNA hybrids, for integration. HIV-1 initiates the formation of R-loops in both genic and non-genic regions of the host genome and preferentially integrates into R-loop-rich regions. Using a cell model that can independently control transcriptional activity and R-loop formation, we demonstrated that the formation of R-loops directs HIV-1 integration targeting sites. We also found that HIV-1 integrase proteins physically bind to the host genomic R-loops. These findings provide fundamental insights into the mechanisms of retroviral integration and the new strategies of antiretroviral therapy against HIV-1 latent infection.","journal":null,"year":2024,"id":498663,"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":0.9515,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":89795,"name":"Dohoon Lee","orcid":"0000-0003-2163-5489","position":1,"is_corresponding":false},{"id":1265465,"name":"Jiseok Jeong","orcid":null,"position":2,"is_corresponding":false},{"id":1345291,"name":"Sungwon Lee","orcid":"0000-0001-6687-0517","position":3,"is_corresponding":false},{"id":89890,"name":"Sun Kim","orcid":"0000-0001-5385-9546","position":4,"is_corresponding":false},{"id":1265013,"name":"Kwangseog Ahn","orcid":"0000-0002-1015-245X","position":5,"is_corresponding":false},{"id":1265011,"name":"Kiwon Park","orcid":"0000-0003-3576-5380","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:09:42.181447Z","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":[]}