ArticleJournal of neurovirology2016
Microglia-derived HIV Nef+ exosome impairment of the blood-brain barrier is treatable by nanomedicine-based delivery of Nef peptides.
Article in Journal of neurovirology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 84 papers.
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Who cites it
84 citing papers in PubMed, 113 citations in OpenAlex.
- The kynurenine pathway in relation to depression and anhedonia symptom severity among women with HIV.Brain, behavior, & immunity - health · 2026Article
- Role of extracellular vesicles derived from HIV-infected T cells and microglial cells in neuroinflammation and neuropathogenesis using a blood-brain barrier and cerebral organoid co-culture model.Journal of neurovirology · 2026Article
- Neuroinflammation and NeuroHIV: understanding the role of HIV-1 related factors in microglial activation.Translational psychiatry · 2026Review
- Review
- Microglia-Derived Extracellular Vesicles from Alzheimer's Disease Patients Carry miRNAs Driving a Neuroinflammatory Response.Molecular neurobiology · 2026Article
- Review
- The prefrontal cortex as a target of HIV-1 neurotoxicity: molecular mechanisms of viral protein-mediated neurodegeneration and executive dysfunction.Frontiers in cellular neuroscience · 2026Review
- Magnetic Nanoparticles and Drug Delivery Systems for Anti-Cancer Applications: A Review.Nanomaterials (Basel, Switzerland) · 2025Review
- HIV protein Nef expression in human microglia drives the release of distinct Nef-containing extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2025Article
- Nef is a key player in neuroinflammation and myelin impairment associated with neuroHIV.Frontiers in neurology · 2025Article
- The Impact of HIV on Early Brain Aging-A Pathophysiological (Re)View.Journal of clinical medicine · 2024Review
- Tumor-derived extracellular vesicles disrupt the blood-brain barrier endothelium following high-frequency irreversible electroporation.Scientific reports · 2024Article
- HIV-Associated Neurocognitive Disorder (HAND) and Alzheimer's Disease Pathogenesis: Future Directions for Diagnosis and Treatment.International journal of molecular sciences · 2024Review
- Structural and Functional Dysregulation of the Brain Endothelium in HIV Infection and Substance Abuse.Cells · 2024Review
- Something to talk about; crosstalk disruption at the neurovascular unit during HIV infection of the CNS.NeuroImmune pharmacology and therapeutics · 2024Article
- HIV-1 RNA in extracellular vesicles is associated with neurocognitive outcomes.Nature communications · 2024Article
- Extracellular vesicles produced by HIV-1 Nef-expressing cells induce myelin impairment and oligodendrocyte damage in the mouse central nervous system.Journal of neuroinflammation · 2024Article
- Microvesicles derived from dermal myofibroblasts modify the integrity of the blood and lymphatic barriers using distinct endocytosis pathways.Journal of extracellular biology · 2024Article
- Recommendations for reproducibility of cerebrospinal fluid extracellular vesicle studies.Journal of extracellular vesicles · 2024Review
- Exploring the role of brain-derived extracellular vesicles in viral infections: from pathological insights to biomarker potential.Frontiers in cellular and infection microbiology · 2024Review
24 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 1 institution in 1 country.
Funding
Abstract
The negative factor (Nef) of human immunodeficiency virus (HIV) is an accessory protein that is thought to be integral to HIV-associated immune- and neuroimmune pathogenesis. Here, we show that nef-transfected microglia-released Nef+ exosome (exNef) disrupts the apical blood-brain barrier (BBB) and that only nef-transfected microglia release Nef in exosomes. nef-gfp-transduced neurons and astrocytes release exosomes but did not release exNef in the extracellular space. Apical administration of exNef derived from nef-transfected 293T cells reduced transendothelial electrical resistance (TEER) and increased permeability of the BBB. Microglia-derived exNef applied to either the apical/basal BBB significantly reduced expression of the tight junction protein, ZO-1, suggesting a mechanism of exNef-mediated neuropathogenesis. Microglia exposed to exNef release elevated levels of Toll-like receptor-induced cytokines and chemokines IL-12, IL-8, IL-6, RANTES, and IL-17A. Magnetic nanoparticle delivery of Nef peptides containing the Nef myrisolation site across an in vitro BBB ultimately reduced nef-transfected microglia release of Nef exosomes and prevented the loss of BBB integrity and permeability as measured by TEER and dextran-FITC transport studies, respectively. Overall, we show that exNef is released from nef-gfp-transfected microglia; exNef disrupts integrity and permeability, and tight junctions of the BBB, and induces microglial cytokine/chemokine secretion. These exNef-mediated effects were significantly restricted by Nef peptides. Taken together, this study provides preliminary evidence of the role of exNef in HIV neuroimmune pathogenesis and the feasibility of a nanomedicine-based therapeutics targeting exNef to treat HIV-associated neuropathogenesis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.