ArticleJournal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology2009
M- and T-tropic HIVs promote apoptosis in rat neurons.
Article in Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Who cites it
31 citing papers in PubMed, 41 citations in OpenAlex.
- Neuropathogenesis of acute HIV: mechanisms, biomarkers, and therapeutic approaches.Current opinion in HIV and AIDS · 2025Review
- Article
- Viral Infections, Are They a Trigger and Risk Factor of Alzheimer's Disease?Pathogens (Basel, Switzerland) · 2024Review
- HIV-1 gp120 Impairs Spatial Memory Through Cyclic AMP Response Element-Binding Protein.Frontiers in aging neuroscience · 2022Article
- Amyloidogenic, neuroinflammatory and memory dysfunction effects of HIV-1 gp120.Archives of pharmacal research · 2021Article
- Alzheimer's disease-like perturbations in HIV-mediated neuronal dysfunctions: understanding mechanisms and developing therapeutic strategies.Open biology · 2020Review
- HIV influences microtubule associated protein-2: potential marker of HIV-associated neurocognitive disorders.AIDS (London, England) · 2020Article
- Histone deacetylase 6 inhibition rescues axonal transport impairments and prevents the neurotoxicity of HIV-1 envelope protein gp120.Cell death & disease · 2019Article
- Reversal of Cognitive Impairment in gp120 Transgenic Mice by the Removal of the p75 Neurotrophin Receptor.Frontiers in cellular neuroscience · 2019Article
- HIV Neuroinfection and Alzheimer's Disease: Similarities and Potential Links?Frontiers in cellular neuroscience · 2018Article
- HIV Associated Neurodegenerative Disorders: A New Perspective on the Role of Lipid Rafts in Gp120-Mediated Neurotoxicity.Current HIV research · 2018Review
- HIV-1 gp120 Upregulates Brain-Derived Neurotrophic Factor (BDNF) Expression in BV2 Cells via the Wnt/β-Catenin Signaling Pathway.Journal of molecular neuroscience : MN · 2017Article
- HIV Glycoprotein Gp120 Impairs Fast Axonal Transport by Activating Tak1 Signaling Pathways.ASN neuro · 2016Article
- Identification of a binding site of the human immunodeficiency virus envelope protein gp120 to neuronal-specific tubulin.Journal of neurochemistry · 2016Article
- HIV-1 gp120Bal down-Regulates Phosphorylated NMDA Receptor Subunit 1 in Cortical Neurons via Activation of Glutamate and Chemokine Receptors.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2016Article
- Pharmacological induction of CCL5 in vivo prevents gp120-mediated neuronal injury.Neuropharmacology · 2015Article
- Synthesis of pyridine derivatives as potential antagonists of chemokine receptor type 4.Heterocyclic communications · 2014Article
- Is human immunodeficiency virus-mediated dementia an autophagic defect that leads to neurodegeneration?CNS & neurological disorders drug targets · 2014Review
- High levels of divergent HIV-1 quasispecies in patients with neurological opportunistic infections in China.Journal of neurovirology · 2013Article
- When human immunodeficiency virus meets chemokines and microglia: neuroprotection or neurodegeneration?Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2013Review
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
Neuronal loss, reactive astrocytes, and other abnormalities are seen in the brain of individuals with acquired immune deficiency syndrome-associated Dementia Complex (ADC). Human immunodeficiency virus-1 (HIV-1) is believed to be the main agent causing ADC. However, little is known about the molecular and cellular mechanisms of HIV-1 neurotoxicity considering that HIV-1 does not infect post-mitotic neurons and that viral load does not necessarily correlate with ADC. Various viral proteins, such as the envelope protein gp120 and the transcription activator Tat, have been shown to induce neuronal apoptosis through direct and indirect mechanisms both in vitro and in vivo. Progeny HIV-1 virions can also cause neuronal death. However, it has not been fully established yet whether HIV-1 promotes neuronal apoptosis by a direct mechanism. To explore the neurotoxic effect of HIV-1, we exposed rat cerebellar granule cells and cortical neurons in culture to two different strains of HIV-1, IIIB and BaL, T- and M-tropic strains that utilize CXCR4 and CCR5 coreceptors, respectively, to infect cells. We observed that both viruses elicit a time-dependent apoptotic cell death in these cultures without inducing a productive infection as determined by the absence of the core protein of HIV-1, p24, in cell lysates. Instead, neurons were gp120 positive, suggesting that the envelope protein is shed by the virus and then subsequently internalized by neurons. The CXCR4 receptor antagonist AMD3100 or the CCR5 receptor inhibitor D-Ala-peptide T-amide blocked HIV IIIB and HIV Bal neurotoxicity, respectively. In contrast, the N-methyl-D-aspartate receptor blocker MK801 failed to protect neurons from HIV-mediated apoptosis, suggesting that HIV-1 neurotoxicity can be initiated by the viral protein gp120 binding to neuronal chemokine receptors.
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