ArticleGlia2019
HIV-1 Tat promotes astrocytic release of CCL2 through MMP/PAR-1 signaling.
Article in Glia, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 33 citations in OpenAlex.
- The relationship between HIV-1 neuroinflammation, neurocognitive impairment and encephalitis pathology: A systematic review of studies investigating post-mortem brain tissue.Reviews in medical virology · 2024Pooled it
- Neuroinflammatory crosstalk between microglia and astrocytes increases viral replication in an iPSC-derived model of CNS HIV infection.Scientific reports · 2026Article
- Review
- Neuroinflammatory crosstalk between microglia and astrocytes increases viral replication in an iPSC-derived model of CNS HIV infection.bioRxiv : the preprint server for biology · 2025Article
- Role of lncRNA Xist-miR-124-CCL2 axis in HIV Tat-mediated microglial activation and neuroinflammation.Frontiers in immunology · 2025Article
- Glutathione in HIV-Associated Neurocognitive Disorders.Current issues in molecular biology · 2024Review
- C-C motif chemokine receptor 2 and 7 synergistically control inflammatory monocyte recruitment but the infecting virus dictates monocyte function in the brain.Communications biology · 2024Article
- Disruption of blood-brain barrier: effects of HIV Tat on brain microvascular endothelial cells and tight junction proteins.Journal of neurovirology · 2023Review
- Evaluation of Proinflammatory Chemokines in HIV Patients with AsymptomaticTropical medicine and infectious disease · 2023Article
- Macrophage migration inhibitory factor facilitates astrocytic production of the CCL2 chemokine following spinal cord injury.Neural regeneration research · 2023Article
- The cytokine/chemokine response inHeliyon · 2023Review
- Role of microglia in HIV-1 infection.AIDS research and therapy · 2023Review
- HIV-Proteins-Associated CNS Neurotoxicity, Their Mediators, and Alternative Treatments.Cellular and molecular neurobiology · 2022Review
- Identification, Quantification, and Characterization of HIV-1 Reservoirs in the Human Brain.Cells · 2022Article
- The potential role of HIV-1 latency in promoting neuroinflammation and HIV-1-associated neurocognitive disorder.Trends in immunology · 2022Review
- Apoptosis-associated speck-like protein containing a CARD-mediated release of matrix metalloproteinase 10 stimulates a change in microglia phenotype.Frontiers in molecular neuroscience · 2022Article
- Reduced neuronal population in the dorsolateral prefrontal cortex in infant macaques infected with simian immunodeficiency virus (SIV).Journal of neurovirology · 2021Article
- HIV Tat-Mediated Induction of Monocyte Transmigration Across the Blood-Brain Barrier: Role of Chemokine Receptor CXCR3.Frontiers in cell and developmental biology · 2021Article
- Cognitive and Neuronal Link With Inflammation: A Longitudinal Study in People With and Without HIV Infection.Journal of acquired immune deficiency syndromes (1999) · 2020Article
- Disruption of auto-inhibition underlies conformational signaling of ASIC1a to induce neuronal necroptosis.Nature communications · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The HIV-1 protein Tat is continually released by HIV-infected cells despite effective combination antiretroviral therapies (cART). Tat promotes neurotoxicity through enhanced expression of proinflammatory molecules from resident and infiltrating immune cells. These molecules include matrix metalloproteinases (MMPs), which are pathologically elevated in HIV, and are known to drive central nervous system (CNS) injury in varied disease settings. A subset of MMPs can activate G-protein coupled protease-activated receptor 1 (PAR-1), a receptor that is highly expressed on astrocytes. Although PAR-1 expression is increased in HIV-associated neurocognitive disorder (HAND), its role in HAND pathogenesis remains understudied. Herein, we explored Tat's ability to induce expression of the PAR-1 agonists MMP-3 and MMP-13. We also investigated MMP/PAR-1-mediated release of CCL2, a chemokine that drives CNS entry of HIV infected monocytes and remains a significant correlate of cognitive dysfunction in the era of cART. Tat exposure significantly increased the expression of MMP-3 and MMP-13. These PAR-1 agonists both stimulated the release of astrocytic CCL2, and both genetic knock-out and pharmacological inhibition of PAR-1 reduced CCL2 release. Moreover, in HIV-infected post-mortem brain tissue, within-sample analyses revealed a correlation between levels of PAR-1-activating MMPs, PAR-1, and CCL2. Collectively, these findings identify MMP/PAR-1 signaling to be involved in the release of CCL2, which may underlie Tat-induced neuroinflammation.
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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.