{"doi":"10.1101/2025.08.07.669137","title":"HIV-1 Infection Regulates Gene Expression by Altering Alternative Polyadenylation Through CPSF6 and CPSF5 Delocalization","abstract":"HIV-1 viral core transport to the nucleus, an early infection event, triggers cleavage and polyadenylation specificity factor (CPSF)5 and CPSF6 to translocate from paraspeckles to nuclear speckles, forming puncta-like structures. CPSF5 and CPSF6 regulate alternative polyadenylation (APA), which governs approximately 70% of gene expression. APA alters the lengths of mRNA 3'-untranslated regions (3'-UTRs), which contain regulatory signals influencing RNA stability, localization, and function. We investigated whether HIV-1 infection-induced changes in CPSF5 and CPSF6 subcellular localization are accompanied by changes in cellular function. Using two independent methodologies to assess APA in human primary CD4+ T cells and cell lines, we found that HIV-1 infection regulates APA, dependent on the interaction of CPSF6 with the viral capsid, recapitulating the APA phenotype observed in CPSF6 knockout cells. Our study demonstrates that HIV-1 infection leverages the interaction between the viral capsid and CPSF6 to co-opt cellular processes, alter gene expression, and drive pathogenesis.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":572308,"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":0.9523,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1392360,"name":"Aihua Dai","orcid":null,"position":1,"is_corresponding":false},{"id":288606,"name":"Hari Krishna Yalamanchili","orcid":"0000-0001-9892-3054","position":2,"is_corresponding":false},{"id":1478950,"name":"Aiswarya Balakrishnan","orcid":null,"position":3,"is_corresponding":false},{"id":250357,"name":"Kai-Lieh Huang","orcid":"0000-0001-5407-648X","position":4,"is_corresponding":false},{"id":814540,"name":"Cinzia Bertelli","orcid":"0000-0002-9443-1957","position":5,"is_corresponding":false},{"id":451705,"name":"Bin Cui","orcid":"0000-0002-0558-9091","position":6,"is_corresponding":false},{"id":283126,"name":"Ramón Lorenzo-Redondo","orcid":"0000-0002-5462-9483","position":7,"is_corresponding":false},{"id":250364,"name":"Eric J. Wagner","orcid":"0000-0003-0217-383X","position":8,"is_corresponding":false},{"id":262616,"name":"Felipe Diaz‐Griffero","orcid":"0000-0002-7021-6152","position":9,"is_corresponding":false},{"id":1056248,"name":"Charlotte Luchsinger","orcid":"0000-0001-6775-7778","position":0,"is_corresponding":true}],"reference_count":59,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:57:23.653298Z","pmid":"40827274","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":[]}