{"doi":"10.1002/jev2.12478","title":"HIV‐1 Nef is carried on the surface of extracellular vesicles","abstract":"Extracellular vesicles (EVs) serve as pivotal mediators of intercellular communication in both health and disease, delivering biologically active molecules from vesicle-producing cells to recipient cells. In the context of HIV infection, EVs have been shown to carry the viral protein Nef, a key pathogenic factor associated with HIV-related co-morbidities. Despite this recognition, the specific localisation of Nef within the vesicles has remained elusive. This study addresses this critical knowledge gap by investigating Nef-containing EVs. Less than 1% of the total released Nef was associated with EVs; most Nef existed as free protein released by damaged cells. Nevertheless, activity of EV-associated Nef in downregulating the major cholesterol transporter ABCA1, a critical aspect linked to the pathogenic effects of Nef, was comparable to that of free Nef present in the supernatant. Through a series of biochemical and microscopic assays, we demonstrate that the majority of EV-associated Nef molecules are localised on the external surface of the vesicles. This distinctive distribution prompts the consideration of Nef-containing EVs as potential targets for immunotherapeutic interventions aimed at preventing or treating HIV-associated co-morbidities. In conclusion, our results shed light on the localisation and functional activity of Nef within EVs, providing valuable insights for the development of targeted immunotherapies to mitigate the impact of HIV-associated co-morbidities.","journal":"Journal of Extracellular Vesicles","year":2024,"id":437008,"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":11,"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":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":869741,"name":"Beda Břicháček","orcid":"0000-0001-5864-4341","position":1,"is_corresponding":false},{"id":477898,"name":"Tatiana Pushkarsky","orcid":null,"position":2,"is_corresponding":false},{"id":343439,"name":"Larisa Dubrovsky","orcid":null,"position":3,"is_corresponding":false},{"id":344428,"name":"Wendy Fitzgerald","orcid":"0000-0001-5752-8250","position":4,"is_corresponding":false},{"id":264534,"name":"Nigora Mukhamedova","orcid":"0000-0002-5924-1816","position":5,"is_corresponding":false},{"id":1246472,"name":"Sofia Garcia‐Hernandez","orcid":null,"position":6,"is_corresponding":false},{"id":259847,"name":"Doreen Matthies","orcid":"0000-0001-9221-4484","position":7,"is_corresponding":false},{"id":311593,"name":"Anastas Popratiloff","orcid":"0000-0002-8329-3907","position":8,"is_corresponding":false},{"id":264533,"name":"Dmitri Sviridov","orcid":"0000-0002-8366-3832","position":9,"is_corresponding":false},{"id":344429,"name":"Leonid Margolis","orcid":"0000-0002-1960-1928","position":10,"is_corresponding":false},{"id":276950,"name":"Michael Bukrinsky","orcid":"0000-0002-8593-0770","position":11,"is_corresponding":false},{"id":620490,"name":"Christophe Vanpouille","orcid":"0000-0002-5791-1409","position":0,"is_corresponding":true}],"reference_count":65,"raw_metadata":null,"created_at":"2026-07-19T02:00:29.872940Z","pmid":"39016173","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":[]}