{"doi":"10.1073/pnas.2418467122","title":"BRD9 functions as an HIV-1 latency regulatory factor","abstract":"<jats:p>\n                    A major challenge for HIV type 1 (HIV-1) cure is the presence of viral latent reservoirs. The “Shock &amp; Kill” strategy involves the combined use of latency reversal agents (LRA) and antiretroviral treatment (ART) to reactivate HIV-1 latent reservoirs, followed by elimination of infected cells. However, current LRAs are insufficient in fully reactivating the latent reservoirs. Therefore, investigation on novel HIV-1 latency regulators will be crucial to the success of HIV-1 cure research. Here, we identify bromodomain-containing protein 9 (BRD9) as an HIV-1 latency regulator. BRD9 inhibition induces HIV-1 latency reactivation in T cell lines, human resting memory CD4\n                    <jats:sup>+</jats:sup>\n                    T cells, and PBMCs derived from people living with HIV-1 (PWH) on ART. BRD9 inhibition, gene depletion, and protein degradation consistently reactivate HIV-1 latency. Moreover, BRD9 inhibition synergizes with BRD4 inhibition in inducing HIV-1 production. Mechanistically, BRD9 binds to HIV-1 LTR promoter and competes with HIV-1 Tat protein for binding to the HIV-1 genome. Additionally, our integrated CUT&amp;RUN DNA sequencing, transcriptomics, and pharmacological analysis revealed downstream host targets of BRD9, including ATAD2 and MTHFD2, that modulate HIV-1 latency.\n                  </jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2025,"id":601990,"datarank":0.3453877639491069,"base_score":2.302585092994046,"endowment":2.302585092994046,"self_citation_contribution":0.3453877639491069,"citation_network_contribution":0.0,"self_endowment_contribution":0.3453877639491069,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":9,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1543714,"name":"Lok-Yan Yim","orcid":null,"position":1,"is_corresponding":false},{"id":1494122,"name":"Runhong Zhou","orcid":"0000-0001-6642-6029","position":2,"is_corresponding":false},{"id":1038062,"name":"Yufei Mo","orcid":"0000-0002-5580-698X","position":3,"is_corresponding":false},{"id":1543716,"name":"Huarong Huang","orcid":"0009-0006-3195-049X","position":4,"is_corresponding":false},{"id":357547,"name":"Meiqing Zhao","orcid":null,"position":5,"is_corresponding":false},{"id":1238267,"name":"Jie Dai","orcid":"0000-0001-9470-5172","position":6,"is_corresponding":false},{"id":1038618,"name":"Thomas Tsz-Kan Lau","orcid":null,"position":7,"is_corresponding":false},{"id":627860,"name":"Xiner Huang","orcid":"0000-0002-0154-8372","position":8,"is_corresponding":false},{"id":336242,"name":"Grace Lui","orcid":"0000-0001-5242-2967","position":9,"is_corresponding":false},{"id":72001,"name":"Kwok-Yung Yuen","orcid":"0000-0001-8700-4570","position":10,"is_corresponding":false},{"id":78570,"name":"Jasper Fuk-Woo Chan","orcid":null,"position":11,"is_corresponding":false},{"id":1543717,"name":"Alfred Sze-Lok Cheng","orcid":null,"position":12,"is_corresponding":false},{"id":105632,"name":"Zhiwei Chen","orcid":"0000-0002-4511-2888","position":13,"is_corresponding":false},{"id":78574,"name":"Hin Chu","orcid":"0000-0003-2855-9837","position":14,"is_corresponding":false},{"id":1543713,"name":"Tsz-Yat Luk","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"BRD9 functions as an HIV-1 latency regulatory factor","abstract":"<jats:p>\n                    A major challenge for HIV type 1 (HIV-1) cure is the presence of viral latent reservoirs. The “Shock &amp; Kill” strategy involves the combined use of latency reversal agents (LRA) and antiretroviral treatment (ART) to reactivate HIV-1 latent reservoirs, followed by elimination of infected cells. However, current LRAs are insufficient in fully reactivating the latent reservoirs. Therefore, investigation on novel HIV-1 latency regulators will be crucial to the success of HIV-1 cure research. Here, we identify bromodomain-containing protein 9 (BRD9) as an HIV-1 latency regulator. BRD9 inhibition induces HIV-1 latency reactivation in T cell lines, human resting memory CD4\n                    <jats:sup>+</jats:sup>\n                    T cells, and PBMCs derived from people living with HIV-1 (PWH) on ART. BRD9 inhibition, gene depletion, and protein degradation consistently reactivate HIV-1 latency. Moreover, BRD9 inhibition synergizes with BRD4 inhibition in inducing HIV-1 production. Mechanistically, BRD9 binds to HIV-1 LTR promoter and competes with HIV-1 Tat protein for binding to the HIV-1 genome. Additionally, our integrated CUT&amp;RUN DNA sequencing, transcriptomics, and pharmacological analysis revealed downstream host targets of BRD9, including ATAD2 and MTHFD2, that modulate HIV-1 latency.\n                  </jats:p>","is_dataset_classified":null,"base_score":0.0,"endowment":0.0,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"40402245","pmcid":"PMC12130862","openalex_id":null,"authors":[],"funders":[{"funder_name":"General Research Fund","grant_id":"17119122","title":null},{"funder_name":"Collaborative Research Fund","grant_id":"C7103-22G","title":null},{"funder_name":"Theme-Based Research Fund","grant_id":"T11-706/18-N","title":null}],"total_grants":3,"fwci":null,"citation_percentile":null,"influential_citations":0,"citation_trend":[],"oa_status":"hybrid","license":"cc-by-nc-nd","oa_locations":[{"url":"https://doi.org/10.1073/pnas.2418467122","host_type":"publisher"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2418467122","host_type":"publisher"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/12130862","host_type":"repository"},{"url":"https://pmc.ncbi.nlm.nih.gov/articles/PMC12130862/","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC12130862","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC12130862?pdf=render","host_type":"Europe_PMC"}],"fields_of_study":[],"mesh_terms":["CD4-Positive T-Lymphocytes","Humans","HIV-1","HIV Infections","Cell Cycle Proteins","Transcription Factors","Virus Latency","Virus Activation","Bromodomain Containing Proteins"],"keywords":["AIDS","Hiv-1 Latency","Brd9"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-07-29T17:57:55.389540Z","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":[]}