ArticleProceedings of the National Academy of Sciences of the United States of America2013
Induction of IL-17 and nonclassical T-cell activation by HIV-Tat protein.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04263207 (Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response in Peripheral Blood HIV Reservoir Dynamics), which is not on this map. Cited by 204 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Observational Study for the Evaluation of the Role of HIV-1 Tat Protein and Anti-Tat Immune Response in Peripheral Blood HIV Reservoir Dynamics
Who cites it
204 citing papers in PubMed, 1 synthesis or guideline pooled it, 256 citations in OpenAlex.
- Patho-immune Mechanisms of Hypertension in HIV: a Systematic and Thematic Review.Current hypertension reports · 2019Pooled it
- Trial
- HIV-1 Tat immunization restores immune homeostasis and attacks the HAART-resistant blood HIV DNA: results of a randomized phase II exploratory clinical trial.Retrovirology · 2015Trial
- ER Stress Regulates HIV Tat and Alcohol-Induced NLRP6 Activation in Astrocytes.CNS neuroscience & therapeutics · 2026Article
- HIV Tat-Stimulated Microglial Extracellular Vesicles Are Enriched for Ferroptosis Mediators: Role of Dysregulated Autophagy.Journal of extracellular biology · 2026Article
- Effects of HIV and azidothymidine on Alzheimer's-like pathology and amyloid beta transporters in hu-PBL-NSG mice, brain endothelial amyloid beta uptake and endothelial barrier integrity.Fluids and barriers of the CNS · 2026Article
- HIV-1 Tat expression drives progressive synaptic decline: evidence from longitudinal [NeuroImmune pharmacology and therapeutics · 2026Article
- HIV Infection, Neurotoxicity, Inflammation, Premature Aging, and Therapeutic Challenges to PLWH: An Overview.International journal of molecular sciences · 2026Review
- HIV-1 Tat and gp120 as key drivers of neurodegeneration in the central nervous system.Frontiers in microbiology · 2026Review
- HIV-1 Tat Protein Exposure Alters the Morphological Characteristics and Gene Expression in the Primary Mouse Cortex Endothelial Cells and Human Brain Microvascular Endothelial Cells.Cellular and molecular neurobiology · 2025Article
- Synthesis and evaluation of novel substituted N-(2-phenylbutyl)-5,6,7,8-tetrahydro-quinazolin-4-amines as allosteric modulators of HIV-DAT-tat interaction.Bioorganic & medicinal chemistry letters · 2025Article
- Mutational effects of the asparagine198 and glutamate223 residues on the human norepinephrine transporter on basal and HIV-1 Tat protein-induced inhibition of dopamine transport.European journal of pharmacology · 2025Article
- HIV-1 Tat protein exposure alters the morphological characteristics and gene expression in the primary mouse cortex endothelial cells and human brain microvascular endothelial cells.Research square · 2025Article
- Sex differences in the capacity of minor phytocannabinoids to attenuate nociceptive insults in HIV-1 Tat-expressing mice.NeuroImmune pharmacology and therapeutics · 2025Article
- HIV-1 Tat favors the multiplication of Mycobacterium tuberculosis and Toxoplasma by inhibiting clathrin-mediated endocytosis and autophagy.PLoS pathogens · 2025Article
- SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes.Life science alliance · 2025Article
- Expression of HIV envelope protein in the human central nervous system.AIDS (London, England) · 2025Article
- Xenon gas as a potential treatment for opioid use disorder, alcohol use disorder, and related disorders.Medical gas research · 2025Review
- Mechanisms of Immune Evasion in HIV-1: The Role of Virus-Host Protein Interactions.Current issues in molecular biology · 2025Review
- HIV-1 Tat protein alters medial prefrontal cortex neuronal activity and recognition memory.iScience · 2025Article
144 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Chronic immune activation is a major complication of antiretroviral therapy (ART) for HIV infection and can cause a devastating immune reconstitution inflammatory syndrome (IRIS) in the brain. The mechanism of T-cell activation in this population is not well understood. We found HIV-Tat protein and IL-17-expressing mononuclear cells in the brain of an individual with IRIS. Tat was also present in the CSF of individuals virologically controlled on ART. Hence we examined if Tat protein could directly activate T cells. Tat transcriptionally dysregulated 94 genes and induced secretion of 11 cytokines particularly activation of IL-17 signaling pathways supporting the development of a proinflammatory state. Tat increased IL-17 transcription and secretion in T cells. Tat entered the T cells rapidly by clathrin-mediated endocytosis and localized to both the cytoplasm and the nucleus. Tat activated T cells through a nonclassical pathway dependent upon vascular endothelial growth factor receptor-2 and downstream secondary signaling pathways but independent of the T-cell receptor. However, Tat stimulation of T cells did not induce T-cell proliferation but increased viral infectivity. This study demonstrates Tat's role as a virulence factor, by driving T-cell activation and contributing to IRIS pathophysiology. This supports the necessity of an anti-Tat therapy in conjunction with ART and identifies multiple targetable pathways to prevent Tat-mediated T-cell activation.
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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.