ArticlePloS one2020
Characterization of Nef expression in different brain regions of SIV-infected macaques.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Review
- Nef is a key player in neuroinflammation and myelin impairment associated with neuroHIV.Frontiers in neurology · 2025Article
- HIV protein Nef expression in human microglia drives the release of distinct Nef-containing extracellular vesicles.Extracellular vesicles and circulating nucleic acids · 2025Article
- Neuroinflammation associated with proviral DNA persists in the brain of virally suppressed people with HIV.Frontiers in immunology · 2025Article
- HIV Protein Nef Induces Cardiomyopathy Through Induction of Bcl2 and p21.International journal of molecular sciences · 2024Article
- Modeling HIV-1 infection and NeuroHIV in hiPSCs-derived cerebral organoid cultures.Journal of neurovirology · 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
- Neuro-HIV-New insights into pathogenesis and emerging therapeutic targets.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2023Article
- NeuN distribution in brain structures of normal and Zika-infected suckling mice.Journal of molecular histology · 2023Article
- HIV Nef Expression Down-modulated GFAP Expression and Altered Glutamate Uptake and Release and Proliferation in Astrocytes.Aging and disease · 2023Article
- The NeuroinflammatoryPotential of HIV-1 NefVariants in Modulating the Gene Expression Profile of Astrocytes.Cells · 2022Article
- Intact HIV Proviruses Persist in the Brain Despite Viral Suppression with ART.Annals of neurology · 2022Article
- Review
- Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain.Cells · 2022Article
- Abundance of Nef and p-Tau217 in Brains of Individuals Diagnosed with HIV-Associated Neurocognitive Disorders Correlate with Disease Severance.Molecular neurobiology · 2022Article
- Longitudinal trajectories of brain volume in combined antiretroviral therapy treated and untreated simian immunodeficiency virus-infected rhesus macaques.AIDS (London, England) · 2021Article
- Advances in SIV/SHIV Non-Human Primate Models of NeuroAIDS.Pathogens (Basel, Switzerland) · 2021Review
- Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
objectiveHIV-associated CNS dysfunction is a significant problem among people with HIV (PWH), who now live longer due to viral suppression from combined anti-retroviral therapy (ART). Over the course of infection, HIV generates toxic viral proteins and induces inflammatory cytokines that have toxic effects on neurons in the CNS. Among these viral proteins, HIV Nef has been found in neurons of postmortem brain specimens from PWH. However, the source of Nef and its impact on neuronal cell homeostasis are still elusive. METHODS AND
resultsHere, in using a simian immunodeficiency virus (SIV) infected rhesus macaque model of neuroHIV, we find SIV Nef reactivity in the frontal cortex, hippocampus and cerebellum of SIV-infected animals using immunohistochemistry (IHC). Interestingly, SIV-infected macaques treated with ART also showed frequent Nef positive cells in the cerebellum and hippocampus. Using dual quantitative RNAscope and IHC, we observed cells that were positive for Nef, but were not for SIV RNA, suggesting that Nef protein is present in cells that are not actively infected with SIV. Using cell specific markers, we observed Nef protein in microglia/macrophages and astrocytes. Importantly, we also identified a number of NeuN-positive neurons, which are not permissive to SIV infection, but contained Nef protein. Further characterization of Nef-positive neurons showed caspase 3 activation, indicating late stage apoptosis in the CNS neurons.
conclusionsOur results suggest that regardless of ART status, Nef is expressed in the brain of SIV infected macaques and may contribute to neurological complications seen in PWH.
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