ArticleJournal of virology2008
Human immunodeficiency virus type 1 Vpr inhibits axonal outgrowth through induction of mitochondrial dysfunction.
Article in Journal of virology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 59 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
- 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
- Microglial Dysfunction and Amyloid-Beta Pathology in Alzheimer's Disease and HIV-Associated Neurocognitive Disorders.International journal of molecular sciences · 2025Review
- Recent advances in discovery and functional analysis of the small proteins and microRNA expressed by polyomaviruses.Virology · 2025Review
- ROS Chronicles in HIV Infection: Genesis of Oxidative Stress, Associated Pathologies, and Therapeutic Strategies.Current issues in molecular biology · 2024Review
- A Rationale and Approach to the Development of Specific Treatments for HIV Associated Neurocognitive Impairment.Microorganisms · 2022Review
- Emerging Role of Nef in the Development of HIV Associated Neurological Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Review
- Characterization of mitochondrial health from human peripheral blood mononuclear cells to cerebral organoids derived from induced pluripotent stem cells.Scientific reports · 2021Article
- Inflammatory Mechanisms and Cascades Contributing to Neurocognitive Impairment in HIV/AIDS.Current topics in behavioral neurosciences · 2021Article
- Subcutaneous Adipocyte Adenosine Triphosphate Levels in HIV Infected Patients.AIDS research and human retroviruses · 2020Article
- Astrocyte activation and altered metabolism in normal aging, age-related CNS diseases, and HAND.Journal of neurovirology · 2019Review
- Mitochondrial biogenesis is altered in HIV+ brains exposed to ART: Implications for therapeutic targeting of astroglia.Neurobiology of disease · 2019Article
- HIV-1 infection alters energy metabolism in the brain: Contributions to HIV-associated neurocognitive disorders.Progress in neurobiology · 2019Review
- Expression of novel proteins by polyomaviruses and recent advances in the structural and functional features of agnoprotein of JC virus, BK virus, and simian virus 40.Journal of cellular physiology · 2019Review
- High content image analysis reveals function of miR-124 upstream of Vimentin in regulating motor neuron mitochondria.Scientific reports · 2018Article
- HIV-1 Vpr disrupts mitochondria axonal transport and accelerates neuronal aging.Neuropharmacology · 2017Article
- Specific amino acids in HIV-1 Vpr are significantly associated with differences in patient neurocognitive status.Journal of neurovirology · 2017Article
- The HIV-1 Vpr Protein: A Multifaceted Target for Therapeutic Intervention.International journal of molecular sciences · 2017Review
- Insulin Treatment Prevents Neuroinflammation and Neuronal Injury with Restored Neurobehavioral Function in Models of HIV/AIDS Neurodegeneration.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2016Article
- HIV-1 gp120-Mediated Mitochondrial Dysfunction and HIV-Associated Neurological Disorders.Neurotoxicity research · 2016Article
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human immunodeficiency virus type 1 (HIV-1)-infected macrophages damage mature neurons in the brain, although their effect on neuronal development has not been clarified. In this study, we show that HIV-1-infected macrophages produce factors that impair the development of neuronal precursor cells and that soluble viral protein R (Vpr) is one of the factors that has the ability to suppress axonal growth. Cell biological analysis revealed that extracellularly administered recombinant Vpr (rVpr) clearly accumulated in mitochondria where a Vpr-binding protein adenine nucleotide translocator localizes and also decreased the mitochondrial membrane potential, which led to ATP synthesis. The depletion of ATP synthesis reduced the transportation of mitochondria within neurites. This mitochondrial dysfunction inhibited axonal growth even when the frequency of apoptosis was not significant. We also found that point mutations of arginine (R) residues to alanine (A) residues at positions 73, 77, and 80 rendered rVpr incapable of causing mitochondrial membrane depolarization and axonal growth inhibition. Moreover, the Vpr-induced inhibition was suppressed after treatment with a ubiquinone analogue (ubiquinone-10). Our results suggest that soluble Vpr is a major viral factor that causes a disturbance in neuronal development through the induction of mitochondrial dysfunction. Since ubiquinone-10 protects the neuronal plasticity in vitro, it may be a therapeutic agent that can offer defense against HIV-1-associated neurological disease.
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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.