ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2007
HIV-1 Vpr causes neuronal apoptosis and in vivo neurodegeneration.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 89 papers.
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Who cites it
89 citing papers in PubMed, 139 citations in OpenAlex.
- Critical role for antiapoptotic Bcl-xL and Mcl-1 in human macrophage survival and cellular IAP1/2 (cIAP1/2) in resistance to HIV-Vpr-induced apoptosis.The Journal of biological chemistry · 2012Trial
- Review
- Neuroinflammatory and Neurodegenerative Roles of HIV-1 Tat: A Review of Recent Evidence.Advances in experimental medicine and biology · 2026Review
- Human immunodeficiency virus 1 glycoprotein 120 induces endoplasmic reticulum stress in neurons.Cell death & disease · 2025Article
- Tat-specific antibodies associated with better HIV-associated motor function.Scientific reports · 2025Article
- Beyond viral suppression: decoding the mitochondrial-immune axis in HIV-associated inflammation and immune dysfunction.Frontiers in cellular and infection microbiology · 2025Review
- HIV-1 Vpu induces neurotoxicity by promoting Caspase 3-dependent cleavage of TDP-43.EMBO reports · 2024Article
- Exploring viral neuropathic pain: Molecular mechanisms and therapeutic implications.PLoS pathogens · 2024Review
- EcoHIV Infection of Primary Murine Brain Cell Cultures to Model HIV Replication and Neuropathogenesis.Viruses · 2024Article
- Spatial Heterogeneity of Brain Lipids in SIV-Infected Macaques Treated with Antiretroviral Therapy.Journal of the American Society for Mass Spectrometry · 2024Article
- Caspase cleavage of gasdermin E causes neuronal pyroptosis in HIV-associated neurocognitive disorder.Brain : a journal of neurology · 2024Article
- Mechanisms underlying HIV-associated cognitive impairment and emerging therapies for its management.Nature reviews. Neurology · 2023Review
- Viral protein R (Vpr)-induced neuroinflammation and its potential contribution to neuronal dysfunction: a scoping review.BMC infectious diseases · 2023Article
- Update on Central Nervous System Effects of HIV in Adolescents and Young Adults.Current HIV/AIDS reports · 2023Review
- A Rationale and Approach to the Development of Specific Treatments for HIV Associated Neurocognitive Impairment.Microorganisms · 2022Review
- Methamphetamine Enhances HIV-Induced Aberrant Proliferation of Neural Progenitor Cells via the FOXO3-Mediated Mechanism.Molecular neurobiology · 2021Article
- Advances in the Experimental Models of HIV-Associated Neurological Disorders.Current HIV/AIDS reports · 2021Review
- Cal'MAM'ity at the Endoplasmic Reticulum-Mitochondrial Interface: A Potential Therapeutic Target for Neurodegeneration and Human Immunodeficiency Virus-Associated Neurocognitive Disorders.Frontiers in neuroscience · 2021Review
- Article
- Endoplasmic reticulum stress and autophagy in HIV-1-associated neurocognitive disorders.Journal of neurovirology · 2020Review
29 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite the introduction of highly active antiretroviral therapy, dementia caused by human immunodeficiency virus-1 (HIV-1) infection remains a devastating and common neurological disorder. Although the mechanisms governing neurodegeneration during HIV-1 infection remain uncertain, the HIV-1 accessory protein, viral protein R (Vpr), has been proposed as a neurotoxic protein. Herein, we report that Vpr protein and transcript were present in the brains of HIV-infected persons. Moreover, soluble Vpr caused neuronal apoptosis, involving cytochrome c extravasation, p53 induction, and activation of caspase-9 while exerting a depressive effect on whole-cell currents in neurons (p < 0.05), which was inhibited by iberiotoxin. Vpr-activated glial cells secreted neurotoxins in a concentration-dependent manner (p < 0.001). Transgenic (Tg) mice expressing Vpr in brain monocytoid cells displayed the transgene principally in the basal ganglia (p < 0.05) and cerebral cortex (p < 0.01) compared with hindbrain expression. Vpr was released from cultured transgenic macrophages, which was cytotoxic to neurons and was blocked by anti-Vpr antibody (p < 0.05). Neuronal injury was observed in Tg animals compared with wild-type littermates, chiefly affecting GAD65 (p < 0.01) and vesicular acetylcholine transferase (p < 0.001) immunopositive neuronal populations in the basal ganglia. There was also a loss of subcortical synaptophysin (p < 0.001) immunoreactivity as well as an increase in activated caspase-3, which was accompanied by a hyperexcitable neurobehavioral phenotype (p < 0.05). Thus, HIV-1 Vpr caused neuronal death through convergent pathogenic mechanisms with ensuing in vivo neurodegeneration, yielding new insights into the mechanisms by which HIV-1 injures the nervous system.
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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.