{"doi":"10.1093/infdis/jiu838","title":"ALIX Rescues Budding of a Double PTAP/PPEY L-Domain Deletion Mutant of Ebola VP40: A Role for ALIX in Ebola Virus Egress","abstract":null,"journal":"Journal of Infectious Diseases","year":2015,"id":686540,"datarank":0.6307038929086449,"base_score":4.204692619390966,"endowment":4.204692619390966,"self_citation_contribution":0.6307038929086449,"citation_network_contribution":0.0,"self_endowment_contribution":0.6307038929086449,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":66,"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":1793613,"name":"Jonathan J. Madara","orcid":null,"position":1,"is_corresponding":false},{"id":1793615,"name":"Yuliang Liu","orcid":null,"position":2,"is_corresponding":false},{"id":1688580,"name":"Wenbo Liu","orcid":null,"position":3,"is_corresponding":false},{"id":155471,"name":"Gordon Ruthel","orcid":null,"position":4,"is_corresponding":false},{"id":155472,"name":"Bruce D. Freedman","orcid":"0000-0003-4487-7210","position":5,"is_corresponding":false},{"id":396775,"name":"Ronald N. Harty","orcid":"0000-0001-6596-0414","position":6,"is_corresponding":false},{"id":398415,"name":"Ziying Han","orcid":null,"position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"ALIX Rescues Budding of a Double PTAP/PPEY L-Domain Deletion Mutant of Ebola VP40: A Role for ALIX in Ebola Virus Egress","abstract":"Ebola (EBOV) is an enveloped, negative-sense RNA virus belonging to the family Filoviridae that causes hemorrhagic fever syndromes with high-mortality rates. To date, there are no licensed vaccines or therapeutics to control EBOV infection and prevent transmission. Consequently, the need to better understand the mechanisms that regulate virus transmission is critical to developing countermeasures. The EBOV VP40 matrix protein plays a central role in late stages of virion assembly and egress, and independent expression of VP40 leads to the production of virus-like particles (VLPs) by a mechanism that accurately mimics budding of live virus. VP40 late (L) budding domains mediate efficient virus-cell separation by recruiting host ESCRT and ESCRT-associated proteins to complete the membrane fission process. L-domains consist of core consensus amino acid motifs including PPxY, P(T/S)AP, and YPx(n)L/I, and EBOV VP40 contains overlapping PPxY and PTAP motifs whose interactions with Nedd4 and Tsg101, respectively, have been characterized extensively. Here, we present data demonstrating for the first time that EBOV VP40 possesses a third L-domain YPx(n)L/I consensus motif that interacts with the ESCRT-III protein Alix. We show that the YPx(n)L/I motif mapping to amino acids 18-26 of EBOV VP40 interacts with the Alix Bro1-V fragment, and that siRNA knockdown of endogenous Alix expression inhibits EBOV VP40 VLP egress. Furthermore, overexpression of Alix Bro1-V rescues VLP production of the budding deficient EBOV VP40 double PTAP/PPEY L-domain deletion mutant to wild-type levels. Together, these findings demonstrate that EBOV VP40 recruits host Alix via a YPx(n)L/I motif that can function as an alternative L-domain to promote virus egress.","is_dataset_classified":null,"base_score":4.204692619390966,"endowment":4.204692619390966,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"25786915","pmcid":"PMC4564528","openalex_id":"https://openalex.org/W2156685362","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI102104","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"T32 AI070077","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI103785","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI103785","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"AI102104","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R33 AI102104","title":null}],"total_grants":6,"fwci":4.8877,"citation_percentile":0.96081285,"influential_citations":0,"citation_trend":[{"year":2015,"count":2},{"year":2016,"count":8},{"year":2017,"count":9},{"year":2018,"count":7},{"year":2019,"count":5},{"year":2020,"count":9},{"year":2021,"count":11},{"year":2022,"count":4},{"year":2023,"count":4},{"year":2024,"count":7}],"oa_status":"closed","license":null,"oa_locations":[{"url":"http://academic.oup.com/jid/article-pdf/212/suppl_2/S138/18083245/jiu838.pdf","host_type":"publisher"},{"url":"https://doi.org/10.1093/infdis/jiu838","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/25786915","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/4564528","host_type":"repository"}],"fields_of_study":["Viral Infections and Outbreaks Research","Neonatal Respiratory Health Research","Neonatal Health and Biochemistry","Amino Acid Motifs","Animals","COS Cells","Calcium-Binding Proteins","Cell Line","Chlorocebus aethiops","Ebolavirus","HEK293 Cells","Hemorrhagic Fever, Ebola","Humans","Protein Interaction Domains and Motifs","Protein Structure, Tertiary","Sequence Deletion","Viral Matrix Proteins","Virus Release"],"mesh_terms":["Animals","Calcium-Binding Proteins","Cell Line","Chlorocebus aethiops","Humans","Viral Matrix Proteins","Sequence Deletion","Protein Structure, Tertiary","Hemorrhagic Fever, Ebola","COS Cells","Amino Acid Motifs","Ebolavirus","Protein Interaction Domains and Motifs","Virus Release","HEK293 Cells"],"keywords":["Ebola virus","VP40","Virology","Biology","Budding","Virus","Genetics","Virus-host interaction","VLPs","Filovirus","Ebola","Escrt","L-domain","Alix"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-18T19:47:36.094982Z","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":[]}