{"doi":"10.17615/v38g-2958","title":"Simian Immunodeficiency Virus-Derived Extracellular Vesicles Induce a Chronic Inflammatory Phenotype in Healthy Astrocytes Unresolved by Anti-Retroviral Therapy","abstract":"Background/Objectives: Extracellular vesicles (EVs) are key mediators of intercellular communication and are implicated in the neuropathogenesis of HIV-associated brain injury (HABI). However, their direct effects on glial cells, particularly in the context of antiretroviral therapy (ART), remain incompletely understood. Methods: In this study, we investigated how EVs from naïve, Simian Immunodeficiency Virus (SIV)-infected, and SIV-infected ART-treated rhesus macaques impact primary mixed glial cultures. Results: Through multiple, sequential applications mimicking chronic exposure, we found that EVs from SIV-infected animals significantly reduced glial expansion and induced a simplified, reactive astrocyte morphology indicative of neuroinflammatory stress. In contrast, EVs from naïve animals supported glial health. EVs derived from ART-treated animals provided partial protection from SIV-induced effects, yet still suppressed glial proliferation and failed to fully restore normal morphology. Furthermore, cytokine profiling revealed that both SIV and SIV + ART EVs induced a sustained proinflammatory secretory phenotype, characterized by elevated IL-6, IL-8, and IFN-γ. Conclusions: Our findings demonstrate that systemically circulating EVs in SIV infection are potential drivers of glial dysfunction. The persistence of these pathogenic EV effects despite ART suggests a vesicle-mediated mechanism that may contribute to chronic neuroinflammation and cognitive impairment in virally suppressed individuals.","journal":"UNC Libraries","year":2025,"id":579935,"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":0.9594,"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":283632,"name":"Tiffany A. Peterson","orcid":null,"position":1,"is_corresponding":false},{"id":302984,"name":"Ryan P. McNamara","orcid":"0000-0002-8866-3532","position":2,"is_corresponding":false},{"id":700277,"name":"Miranda D. Horn","orcid":"0000-0001-9950-8418","position":3,"is_corresponding":false},{"id":472898,"name":"Matilda J. Moström","orcid":"0000-0001-7261-6638","position":4,"is_corresponding":false},{"id":334457,"name":"Yijun Zhou","orcid":"0000-0002-0585-2689","position":5,"is_corresponding":false},{"id":282162,"name":"Andrew G. MacLean","orcid":"0000-0002-0356-0674","position":6,"is_corresponding":false},{"id":1113310,"name":"Alison R. Van Zandt","orcid":"0000-0002-2773-101X","position":7,"is_corresponding":false},{"id":1490795,"name":"Frost, Elise M.","orcid":null,"position":8,"is_corresponding":false},{"id":1489808,"name":"Blake Schoest","orcid":null,"position":9,"is_corresponding":false},{"id":295812,"name":"Dirk P. Dittmer","orcid":"0000-0003-4968-5656","position":10,"is_corresponding":false},{"id":259617,"name":"Nicholas J. Maness","orcid":"0000-0002-9332-7891","position":0,"is_corresponding":true}],"reference_count":0,"raw_metadata":null,"created_at":"2026-07-19T02:58:34.718602Z","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":[]}