{"doi":"10.1101/2025.11.19.689067","title":"Dengue Virus NS1 Binds Ephrin B1 to Trigger Endothelial Dysfunction","abstract":"Abstract Dengue virus (DENV), a member of the Flaviviridae family, is the most prevalent and medically important mosquito-borne viral pathogen. Infected cells secrete the viral non-structural protein 1 (NS1) into the bloodstream, where it can interact with endothelial cells to induce vascular leak. Host factors involved in NS1-mediated endothelial dysfunction are incompletely understood, leading us to investigate the host interactome of DENV NS1 in endothelial cells via a comparative mass spectrometry approach. We identified ephrin B1 (EFNB1) as a critical host factor in NS1-mediated endothelial barrier dysfunction and show that phosphorylation of EFNB1 is necessary for induction of barrier dysfunction. Further, we map the interface of the EFNB1-NS1 complex through biochemical and computational approaches, and we show that EFNB1-Fc-fusion proteins can act as decoys to block NS1-induced barrier dysfunction in vitro and in vivo . This study provides insights into the mechanism of flavivirus NS1-mediated endothelial barrier dysfunction and new avenues to target vascular leak.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":559533,"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":1,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9588,"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":1195102,"name":"Sabrina Hammond","orcid":null,"position":1,"is_corresponding":false},{"id":1460790,"name":"Charlotte Flory","orcid":"0000-0001-5049-6380","position":2,"is_corresponding":false},{"id":1329508,"name":"Xinyi Feng","orcid":"0000-0001-5960-1028","position":3,"is_corresponding":false},{"id":1460791,"name":"S. Lee","orcid":"0009-0004-0662-5607","position":4,"is_corresponding":false},{"id":934004,"name":"Erika Vanessa Jiménez-Posada","orcid":"0000-0002-3737-9427","position":5,"is_corresponding":false},{"id":242449,"name":"Elias Duarte","orcid":"0000-0003-2541-5504","position":6,"is_corresponding":false},{"id":794008,"name":"Jaime A. Cardona‐Ospina","orcid":"0000-0003-3996-2293","position":7,"is_corresponding":false},{"id":744739,"name":"Aquena H. Ball","orcid":"0009-0002-7193-5738","position":8,"is_corresponding":false},{"id":540191,"name":"N. Lee","orcid":null,"position":9,"is_corresponding":false},{"id":1461353,"name":"Kayla Leung","orcid":null,"position":10,"is_corresponding":false},{"id":854586,"name":"Laurentia V. Tjang","orcid":"0000-0003-0949-3713","position":11,"is_corresponding":false},{"id":627586,"name":"P. Robert Beatty","orcid":"0000-0003-1645-2880","position":12,"is_corresponding":false},{"id":355504,"name":"Scott B. Biering","orcid":"0000-0003-1991-629X","position":13,"is_corresponding":false},{"id":1231314,"name":"Pietro Scaturro","orcid":"0000-0001-9098-3087","position":14,"is_corresponding":false},{"id":236674,"name":"Eva Harris","orcid":"0000-0002-7238-4037","position":15,"is_corresponding":false},{"id":854587,"name":"Felix Pahmeier","orcid":"0000-0002-7445-2259","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":null,"created_at":"2026-07-19T02:55:34.849815Z","pmid":"41332748","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":[]}