ArticleNeurobiology of disease2007
Human immunodeficiency virus type-1 protein Tat induces tumor necrosis factor-alpha-mediated neurotoxicity.
Article in Neurobiology of disease, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 60 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
60 citing papers in PubMed, 67 citations in OpenAlex.
- Trial
- HIV Tat-activated microglial extracellular vesicles induce neuronal iron dysregulation and synaptodendritic injury.Cell communication and signaling : CCS · 2026Article
- Neuroinflammatory and Neurodegenerative Roles of HIV-1 Tat: A Review of Recent Evidence.Advances in experimental medicine and biology · 2026Review
- SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes.Life science alliance · 2025Article
- Neurovirulent and non-neurovirulent strains of HIV-1 and their Tat proteins induce differential cytokine-chemokine profiles.NeuroImmune pharmacology and therapeutics · 2025Article
- HIV Tat as a latency reversing agent: turning the tables on viral persistence.Frontiers in immunology · 2025Review
- Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2.International journal of molecular sciences · 2024Article
- Cerebrospinal fluid CD14Journal of neurovirology · 2023Article
- Structural Insights into the Mechanism of HIV-1 Tat Secretion from the Plasma Membrane.Journal of molecular biology · 2023Article
- Insights Into the Role of Mortalin in Alzheimer's Disease, Parkinson's Disease, and HIV-1-Associated Neurocognitive Disorders.Frontiers in cell and developmental biology · 2022Review
- Antiretroviral Drugs Promote Amyloidogenesis by De-Acidifying Endolysosomes.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2021Article
- The versatile role of exosomes in human retroviral infections: from immunopathogenesis to clinical application.Cell & bioscience · 2021Review
- HIV-Associated Neurotoxicity: The Interplay of Host and Viral Proteins.Mediators of inflammation · 2021Review
- Functional impact of HIV-1 Tat on cells of the CNS and its role in HAND.Cellular and molecular life sciences : CMLS · 2020Review
- HIV-1 Tat-Induced Astrocytic Extracellular Vesicle miR-7 Impairs Synaptic Architecture.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2020Article
- Inflammation-induced PINCH expression leads to actin depolymerization and mitochondrial mislocalization in neurons.Translational neurodegeneration · 2020Article
- Role of endolysosomes and inter-organellar signaling in brain disease.Neurobiology of disease · 2020Review
- Advances toward Curing HIV-1 Infection in Tissue Reservoirs.Journal of virology · 2020Review
- Extracellular HIV-1 Tat Mediates Increased Glutamate in the CNS Leading to Onset of Senescence and Progression of HAND.Frontiers in aging neuroscience · 2020Review
- Readily Releasable Stores of Calcium in Neuronal Endolysosomes: Physiological and Pathophysiological Relevance.Advances in experimental medicine and biology · 2020Review
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
HIV-1 infection causes, with increasing prevalence, neurological disorders characterized in part by neuronal cell death. The HIV-1 protein Tat has been shown to be directly and indirectly neurotoxic. Here, we tested the hypothesis that a non-neurotoxic epitope of Tat can, through actions on immune cells, increase neuronal cell death. Tat(1-72) and a mutant Tat(1-72) lacking the neurotoxic epitope (Tat(Delta31-61)) concentration-dependently and markedly increased TNF-alpha production in macrophage-like differentiated human U937 and THP-1 cells, in mouse peritoneal macrophages and in mouse brain microglia. Tat(1-72) was but Tat(Delta31-61) was not neurotoxic when applied directly to neurons. Supernatants from U937 cells treated with either Tat(1-72) or Tat(Delta31-61) were neurotoxic and their immunoneutralization with an anti-TNF-alpha antibody decreased Tat(1-72)- and Tat(Delta31-61)-induced neurotoxicity. Together, these results demonstrate that the neurotoxic epitope of Tat(1-72) is different from the epitope that is indirectly neurotoxic following production of TNF-alpha from immune cells, and suggest that therapeutic interventions against TNF-alpha might be beneficial against HIV-1 associated neurological disorders.
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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.