{"doi":"10.1073/pnas.2133846100","title":"Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins","abstract":"<jats:p>The release of enveloped viruses from infected cells often requires a virally encoded activity, termed a late-budding domain (L domain), encoded by essential PTAP, PPXY, or YPDL sequence motifs. PTAP-type L domains recruit one of three endosomal sorting complexes required for transport (ESCRT-I). However, subsequent events in viral budding are poorly defined, and neither YPDL nor PPXY-type L domains require ESCRT-I. Here, we show that ESCRT-I and other class E vacuolar protein sorting (VPS) factors are linked by a complex series of protein–protein interactions. In particular, interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX, a mammalian orthologue of the yeast class E VPS factor, Bro1. Expression of certain ESCRT-III components as fusion proteins induces a late budding defect that afflicts all three L-domain types, suggesting that ESCRT-III integrity is required in a general manner. Notably, the prototype YPDL-type L domain encoded by equine infectious anemia virus (EIAV) acts by recruiting AIP-1/ALIX and expression of a truncated form of AIP-1/ALIX or small interfering RNA-induced AIP-1/ALIX depletion specifically inhibits EIAV YPDL-type L-domain function. Overall, these findings indicate that L domains subvert a subset of class E VPS factors to mediate viral budding, some of which are required for each of the L-domain types, whereas others apparently act as adaptors to physically link specific L-domain types to the class E VPS machinery.</jats:p>","journal":"Proceedings of the National Academy of Sciences","year":2003,"id":682690,"datarank":0.8968328647351684,"base_score":5.978885764901122,"endowment":5.978885764901122,"self_citation_contribution":0.8968328647351684,"citation_network_contribution":0.0,"self_endowment_contribution":0.8968328647351684,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":394,"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":1783472,"name":"Anton Yaravoy","orcid":null,"position":1,"is_corresponding":false},{"id":1783474,"name":"David Perez-Caballero","orcid":null,"position":2,"is_corresponding":false},{"id":16992,"name":"Paul D. Bieniasz","orcid":"0000-0002-2368-3719","position":3,"is_corresponding":false},{"id":201621,"name":"Juan Martin-Serrano","orcid":"0000-0002-8183-3914","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Divergent retroviral late-budding domains recruit vacuolar protein sorting factors by using alternative adaptor proteins","abstract":"<jats:p>The release of enveloped viruses from infected cells often requires a virally encoded activity, termed a late-budding domain (L domain), encoded by essential PTAP, PPXY, or YPDL sequence motifs. PTAP-type L domains recruit one of three endosomal sorting complexes required for transport (ESCRT-I). However, subsequent events in viral budding are poorly defined, and neither YPDL nor PPXY-type L domains require ESCRT-I. Here, we show that ESCRT-I and other class E vacuolar protein sorting (VPS) factors are linked by a complex series of protein–protein interactions. In particular, interactions between ESCRT-I and ESCRT-III are bridged by AIP-1/ALIX, a mammalian orthologue of the yeast class E VPS factor, Bro1. Expression of certain ESCRT-III components as fusion proteins induces a late budding defect that afflicts all three L-domain types, suggesting that ESCRT-III integrity is required in a general manner. Notably, the prototype YPDL-type L domain encoded by equine infectious anemia virus (EIAV) acts by recruiting AIP-1/ALIX and expression of a truncated form of AIP-1/ALIX or small interfering RNA-induced AIP-1/ALIX depletion specifically inhibits EIAV YPDL-type L-domain function. Overall, these findings indicate that L domains subvert a subset of class E VPS factors to mediate viral budding, some of which are required for each of the L-domain types, whereas others apparently act as adaptors to physically link specific L-domain types to the class E VPS machinery.</jats:p>","is_dataset_classified":null,"base_score":5.978885764901122,"endowment":5.978885764901122,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"14519844","pmcid":"PMC218772","openalex_id":"https://openalex.org/W2123460928","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI050111","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI 52774","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI 50111","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI052774","title":null}],"total_grants":4,"fwci":9.7412,"citation_percentile":0.99035321,"influential_citations":0,"citation_trend":[{"year":2012,"count":16},{"year":2013,"count":16},{"year":2014,"count":10},{"year":2015,"count":11},{"year":2016,"count":11},{"year":2017,"count":5},{"year":2018,"count":16},{"year":2019,"count":15},{"year":2020,"count":15},{"year":2021,"count":11},{"year":2022,"count":10},{"year":2023,"count":11},{"year":2024,"count":5},{"year":2025,"count":6},{"year":2026,"count":7}],"oa_status":"green","license":null,"oa_locations":[{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/218772","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/218772","host_type":"repository"},{"url":"https://pnas.org/doi/pdf/10.1073/pnas.2133846100","host_type":"publisher"},{"url":"https://doi.org/10.1073/pnas.2133846100","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/14519844","host_type":"repository"},{"url":"https://kclpure.kcl.ac.uk/portal/en/publications/b2a1a657-7d90-4343-b292-9940ec378177","host_type":"repository"}],"fields_of_study":["Cellular transport and secretion","HIV Research and Treatment","Mosquito-borne diseases and control","Animals","Calcium-Binding Proteins","Carrier Proteins","Cell Cycle Proteins","Cell Line","Endosomal Sorting Complexes Required for Transport","Humans","Microscopy, Electron","Protein Binding","RNA, Small Interfering","Recombinant Proteins","Retroviridae","Two-Hybrid System Techniques","Vacuoles"],"mesh_terms":["Animals","Calcium-Binding Proteins","Carrier Proteins","Cell Line","Humans","Microscopy, Electron","Protein Binding","Recombinant Proteins","Retroviridae","Vacuoles","Cell Cycle Proteins","Two-Hybrid System Techniques","RNA, Small Interfering","Endosomal Sorting Complexes Required for Transport"],"keywords":["ESCRT","Vacuolar protein sorting","Biology","Endosome","Budding","Cell biology","TSG101","Protein domain","Signal transducing adaptor protein","Virology","Genetics","Gene","Signal transduction","Microvesicles"],"sdg_mappings":[],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[{"name":"gen"}],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-17T21:06:39.067725Z","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":[]}