{"doi":"10.1371/journal.ppat.1011492","title":"HIV-1 virological synapse formation enhances infection spread by dysregulating Aurora Kinase B","abstract":"HIV-1 spreads efficiently through direct cell-to-cell transmission at virological synapses (VSs) formed by interactions between HIV-1 envelope proteins (Env) on the surface of infected cells and CD4 receptors on uninfected target cells. Env-CD4 interactions bring the infected and uninfected cellular membranes into close proximity and induce transport of viral and cellular factors to the VS for efficient virion assembly and HIV-1 transmission. Using novel, cell-specific stable isotope labeling and quantitative mass spectrometric proteomics, we identified extensive changes in the levels and phosphorylation states of proteins in HIV-1 infected producer cells upon mixing with CD4+ target cells under conditions inducing VS formation. These coculture-induced alterations involved multiple cellular pathways including transcription, TCR signaling and, unexpectedly, cell cycle regulation, and were dominated by Env-dependent responses. We confirmed the proteomic results using inhibitors targeting regulatory kinases and phosphatases in selected pathways identified by our proteomic analysis. Strikingly, inhibiting the key mitotic regulator Aurora kinase B (AURKB) in HIV-1 infected cells significantly increased HIV activity in cell-to-cell fusion and transmission but had little effect on cell-free infection. Consistent with this, we found that AURKB regulates the fusogenic activity of HIV-1 Env. In the Jurkat T cell line and primary T cells, HIV-1 Env:CD4 interaction also dramatically induced cell cycle-independent AURKB relocalization to the centromere, and this signaling required the long (150 aa) cytoplasmic C-terminal domain (CTD) of Env. These results imply that cytoplasmic/plasma membrane AURKB restricts HIV-1 envelope fusion, and that this restriction is overcome by Env CTD-induced AURKB relocalization. Taken together, our data reveal a new signaling pathway regulating HIV-1 cell-to-cell transmission and potential new avenues for therapeutic intervention through targeting the Env CTD and AURKB activity.","journal":"PLoS Pathogens","year":2023,"id":359607,"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":10,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9493,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1110550,"name":"Eunju Park","orcid":"0000-0002-4251-2739","position":1,"is_corresponding":false},{"id":753090,"name":"Chris S. Magnano","orcid":null,"position":2,"is_corresponding":false},{"id":457998,"name":"Mark Horswill","orcid":null,"position":3,"is_corresponding":false},{"id":1472,"name":"Alicia Richards","orcid":"0000-0002-4869-2945","position":4,"is_corresponding":false},{"id":547121,"name":"Gregory K. Potts","orcid":"0000-0003-0542-9781","position":5,"is_corresponding":false},{"id":578390,"name":"Alexander S. Hebert","orcid":"0000-0003-4882-2241","position":6,"is_corresponding":false},{"id":1111107,"name":"Nafisah Islam","orcid":null,"position":7,"is_corresponding":false},{"id":71208,"name":"Joshua J. Coon","orcid":"0000-0002-0004-8253","position":8,"is_corresponding":false},{"id":6576,"name":"Anthony Gitter","orcid":"0000-0002-5324-9833","position":9,"is_corresponding":false},{"id":461939,"name":"Nathan M. Sherer","orcid":"0000-0001-9974-236X","position":10,"is_corresponding":false},{"id":456752,"name":"Paul Ahlquist","orcid":"0000-0003-4584-9318","position":11,"is_corresponding":false},{"id":1110549,"name":"James W. Bruce","orcid":"0000-0002-4323-2966","position":0,"is_corresponding":true}],"reference_count":131,"raw_metadata":null,"created_at":"2026-07-19T01:13:57.361401Z","pmid":"37459363","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":[]}