Astragalus polysaccharide-linked exosomes “wake up” latent HIV-1 by flipping a key cellular switch

Latent HIV-1 reservoirs remain a central obstacle to a functional cure because the virus can persist silently in infected cells despite antiretroviral therapy. “Shock-and-kill” strategies aim to reactivate (“shock”) latent virus so infected cells become visible to immune clearance or additional therapies, but clinically safe and effective latency-reversing approaches are still limited.

In this study, researchers investigated whether exosomes could mediate latency reversal after exposure to Astragalus polysaccharide (APS). Using the HIV-1 latency model J-Lat Full Length 10.6, they generated exosomes from APS-treated reservoir cells (APS-Lat-EXO) and compared them with exosomes from untreated cells (Lat-EXO). When applied to recipient cells, APS-Lat-EXO significantly enhanced HIV-1 reactivation, assessed by increased GFP⁺ proportions (flow cytometry), elevated p24 levels (ELISA), and upregulated Gag/LTR transcripts (RT-qPCR). Similar reactivation signals were also observed in PBMCs from HIV-1-infected individuals.

Proteomic and miRNA profiling revealed distinct exosomal cargo after APS exposure, with enrichment pointing to PI3K/AKT and links to NF-κB regulation. Western blot validation supported activation of the PI3K/AKT/NF-κB axis, consistent with transcriptional reawakening of latent HIV-1. These findings highlight APS-Lat-EXO as a bio-derived, mechanistically defined candidate to support latency-reversal research within the shock-and-kill framework.

The work titled “Astragalus polysaccharide promotes latent HIV-1 reactivation via exosome-mediated modulation of the PI3K/AKT/NF-κB axis”, was published on Extracellular Vesicles and Circulating Nucleic Acids (published on January 29, 2026).