{"doi":"10.1101/2022.06.24.497538","title":"Extracellular vesicles carrying HIV-1 Nef induce trained immunity in myeloid cells","abstract":"Summary Persistent inflammation is a hallmark of HIV infection and is not reversed after suppression of viral replication by anti-retroviral therapy (ART). One explanation for chronic inflammation in ART-treated HIV-infected individuals is hyperreactivity of the myeloid cells due to a phenomenon called ‘trained immunity’. Here, we demonstrate that human monocyte derived macrophages originating from monocytes initially treated with extracellular vesicles containing HIV-1 protein Nef (exNef), but differentiating in the absence of exNef, released increased levels of pro-inflammatory cytokines after lipopolysaccharide stimulation. This effect was associated with epigenetic changes related to inflammation and cholesterol metabolism pathways, upregulation of the lipid rafts, and was blocked by methyl-β-cyclodextrin, statin, and inhibitor of activity of lipid raft-associated receptor IGF1R. Bone marrow-derived macrophages from exNef-injected mice had higher abundance of lipid rafts and produced elevated levels of TNFα. These phenomena are consistent with trained immunity and may contribute to persistent inflammation and co-morbidities in HIV-infected individuals.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2022,"id":309542,"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":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9543,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","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":89987,"name":"N. M. Prashant","orcid":"0000-0003-3548-5637","position":2,"is_corresponding":false},{"id":477898,"name":"Tatiana Pushkarsky","orcid":null,"position":3,"is_corresponding":false},{"id":264534,"name":"Nigora Mukhamedova","orcid":"0000-0002-5924-1816","position":4,"is_corresponding":false},{"id":256898,"name":"Dragana Dragoljevic","orcid":null,"position":5,"is_corresponding":false},{"id":29021,"name":"Michael G. FitzGerald","orcid":"0000-0002-0488-0530","position":6,"is_corresponding":false},{"id":367503,"name":"Anélia Horvath","orcid":"0000-0003-4117-013X","position":7,"is_corresponding":false},{"id":254370,"name":"Andrew Murphy","orcid":"0000-0001-7039-7777","position":8,"is_corresponding":false},{"id":264533,"name":"Dmitri Sviridov","orcid":"0000-0002-8366-3832","position":9,"is_corresponding":false},{"id":276950,"name":"Michael Bukrinsky","orcid":"0000-0002-8593-0770","position":10,"is_corresponding":false},{"id":343439,"name":"Larisa Dubrovsky","orcid":null,"position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T00:33:11.579763Z","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":[]}