MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease

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HIV associated neurocognitive disorder (HAND) are neurological disorders caused due to the entry of HIV infection in the brain. HIV-1 does not directly infect central or peripheral neurons, however, virus-infected cells of the monocyte/macrophage lineage maintain a low-level HIV infection in the CNS. "Indirect effects" of macrophage activation–such as dysregulation of cytokines and chemokines, free-radical (oxidative stress) injury, and secretion of soluble factors that are potently neurotoxic–have been implicated as effectors of nervous system injury in HIV. Here, we report that extracellular vesicles released from macrophages can enhance neurotoxicity. Using a nonhuman primate model of HAND, simian immunodeficiency virus encephalitis (SIVE), we find that exosomes isolated from SIVE brains contain,microRNAs, including miR-21, that can serve as ligands to the key immune regulatory receptors, toll-like receptors, and can elicit neurotoxicity. We provide in vitro evidence for such an effect, and that the toxicity can be mediated by necroptosis. Thus, our study provides insights into other potential neurotoxic mechanisms by which HIV infection in the brain could harm neuronal health.

Vyšlo v časopise: MiR-21 in Extracellular Vesicles Leads to Neurotoxicity via TLR7 Signaling in SIV Neurological Disease. PLoS Pathog 11(7): e32767. doi:10.1371/journal.ppat.1005032
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005032

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