{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T20:06:13Z","timestamp":1769717173803,"version":"3.49.0"},"reference-count":55,"publisher":"OAE Publishing Inc.","issue":"1","content-domain":{"domain":["oaepublish.com"],"crossmark-restriction":false},"short-container-title":["Extracell Vesicles Circ Nucleic Acids."],"abstract":"<jats:p>Aim: Reactivating the human immunodeficiency virus type 1 (HIV-1) reservoir is one of the key avenues toward a functional cure for acquired immunodeficiency syndrome (AIDS). However, clinically effective and safe latency-reversing agents remain lacking. Exosomes play an important role in regulating latent HIV-1. This study elucidates the capacity of exosomes derived from Astragalus polysaccharide (APS)-primed HIV-1 reservoir cells, J-Lat Full Length 10.6 (hereafter abbreviated as J-Lat 10.6), termed APS-Lat-EXO, to reactivate latent HIV-1 and investigates the underlying mechanisms.<\/jats:p>\n                  <jats:p>Methods: J-Lat 10.6 cells were used as a model of HIV-1 latency. Cells were exposed to APS, and exosomes derived from APS-treated cells (APS-Lat-EXO) and untreated cells (Lat-EXO) were isolated. These exosomes were subsequently applied to J-Lat 10.6 cells. Latency reactivation was evaluated by flow cytometry, Enzyme-Linked ImmunoSorbent Assay (ELISA), and real-time quantitative polymerase chain reaction (RT-qPCR), which measured green fluorescent protein (GFP\u207a) cell proportions, p24 (the HIV-1 capsid protein) levels, and group-specific antigen (Gag)\/long terminal repeat (LTR) expression, respectively. Proteomic and microRNAs (miRNAs) analyses were performed to compare APS-Lat-EXO and Lat-EXO, and Western blot assays were used to assess activation of the phosphoinositide 3-kinase (PI3K)\/protein kinase B (AKT)\/nuclear factor kappa-light-chain-enhancer of activated B cells (NF-\u03baB) signaling pathway.<\/jats:p>\n                  <jats:p>Results: APS-Lat-EXO significantly reactivated latent HIV reservoirs in both J-Lat 10.6 cells and peripheral blood mononuclear cells from HIV-1-infected individuals, as indicated by increased GFP\u207a cell proportions, elevated p24 levels, and upregulated Gag\/LTR expression. Proteomic and miRNA microarray analyses revealed notable differences between APS-Lat-EXO and Lat-EXO in protein profiles and miRNA composition. Functional enrichment analyses showed that differentially expressed proteins in APS-Lat-EXO were enriched in the PI3K\/AKT pathway, while differentially expressed miRNAs were linked to NF-\u03baB. In vitro experiments confirmed that APS-Lat-EXO reactivated latent HIV-1 via the PI3K\/AKT\/NF-\u03baB pathway.<\/jats:p>\n                  <jats:p>Conclusion: This study shows that APS-Lat-EXO is capable of inducing reactivation of latent HIV-1 through activation of the PI3K\/AKT\/NF-\u03baB axis, highlighting its potential as a bio-derived latency-reversing candidate within the shock-and-kill framework.<\/jats:p>","DOI":"10.20517\/evcna.2025.148","type":"journal-article","created":{"date-parts":[[2026,1,29]],"date-time":"2026-01-29T09:33:51Z","timestamp":1769679231000},"page":"94-113","update-policy":"https:\/\/doi.org\/10.20517\/oae.crossmark.policy","source":"Crossref","is-referenced-by-count":0,"title":["Astragalus polysaccharide promotes latent HIV-1 reactivation via exosome-mediated modulation of the PI3K\/AKT\/NF-\u03baB 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