ArticleThe Journal of biological chemistry2016
HIV-1 Tat Induces Unfolded Protein Response and Endoplasmic Reticulum Stress in Astrocytes and Causes Neurotoxicity through Glial Fibrillary Acidic Protein (GFAP) Activation and Aggregation.
Article in The Journal of biological chemistry, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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Who cites it
56 citing papers in PubMed, 76 citations in OpenAlex.
- Neuroinflammatory and Neurodegenerative Roles of HIV-1 Tat: A Review of Recent Evidence.Advances in experimental medicine and biology · 2026Review
- Chronic Neuroplasticity Changes Following Neurotropic Viral Infection: Mechanisms and Implications.Cellular and molecular neurobiology · 2025Review
- Hantaan virus infection induces human mucosal-associated invariant T cell pyroptosis through IRE1α pathway.Communications biology · 2025Article
- Viruses and psychiatric disorders: We have not crossed the borderline from hypothesis to proof yet (Review).Molecular medicine reports · 2025Review
- Nef mediates neuroimmune response, myelin impairment, and neuronal injury in EcoHIV-infected mice.Life science alliance · 2025Article
- Acute Administration of HIV-1 Tat Protein Drives Glutamatergic Alterations in a Rodent Model of HIV-Associated Neurocognitive Disorders.Molecular neurobiology · 2024Article
- HIV-1 and methamphetamine co-treatment in primary human astrocytes: TAARgeting ER/UPR dysfunction.NeuroImmune pharmacology and therapeutics · 2024Article
- Genetic Variations in EIF2AK3 are Associated with Neurocognitive Impairment in People Living with HIV.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2024Article
- Molecular Mechanisms Associated with Neurodegeneration of Neurotropic Viral Infection.Molecular neurobiology · 2024Review
- Disruption of blood-brain barrier: effects of HIV Tat on brain microvascular endothelial cells and tight junction proteins.Journal of neurovirology · 2023Review
- 4-Phenyl-butyric Acid Inhibits Japanese Encephalitis Virus Replication via Inhibiting Endoplasmic Reticulum Stress Response.Viruses · 2023Article
- HIV Nef Expression Down-modulated GFAP Expression and Altered Glutamate Uptake and Release and Proliferation in Astrocytes.Aging and disease · 2023Article
- PKR-like ER kinase (PERK) Haplotypes Are Associated with Depressive Symptoms in People with HIV.Journal of neurology and psychology · 2023Article
- The Epigenetic Role of miR-124 in HIV-1 Tat- and Cocaine-Mediated Microglial Activation.International journal of molecular sciences · 2022Article
- Glial Fibrillary Acidic Protein: A Biomarker and Drug Target for Alzheimer's Disease.Pharmaceutics · 2022Article
- West Nile Virus Neuroinfection in Humans: Peripheral Biomarkers of Neuroinflammation and Neuronal Damage.Viruses · 2022Article
- Review
- Astrocyte Activation is A Potential Mechanism Underlying Depressed Mood and Apathy in People with HIV.Journal of neurology and psychology · 2022Article
- Why antidiabetic drugs are potentially neuroprotective during the Sars-CoV-2 pandemic: The focus on astroglial UPR and calcium-binding proteins.Frontiers in cellular neuroscience · 2022Review
- A Non-Canonical Role for IRE1α Links ER and Mitochondria as Key Regulators of Astrocyte Dysfunction: Implications in Methamphetamine use and HIV-Associated Neurocognitive Disorders.Frontiers in neuroscience · 2022Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
Abstract
HIV-1 Tat is a major culprit for HIV/neuroAIDS. One of the consistent hallmarks of HIV/neuroAIDS is reactive astrocytes or astrocytosis, characterized by increased cytoplasmic accumulation of the intermediate filament glial fibrillary acidic protein (GFAP). We have shown that that Tat induces GFAP expression in astrocytes and that GFAP activation is indispensable for astrocyte-mediated Tat neurotoxicity. However, the underlying molecular mechanisms are not known. In this study, we showed that Tat expression or GFAP expression led to formation of GFAP aggregates and induction of unfolded protein response (UPR) and endoplasmic reticulum (ER) stress in astrocytes. In addition, we demonstrated that GFAP up-regulation and aggregation in astrocytes were necessary but also sufficient for UPR/ER stress induction in Tat-expressing astrocytes and for astrocyte-mediated Tat neurotoxicity. Importantly, we demonstrated that inhibition of Tat- or GFAP-induced UPR/ER stress by the chemical chaperone 4-phenylbutyrate significantly alleviated astrocyte-mediated Tat neurotoxicity in vitro and in the brain of Tat-expressing mice. Taken together, these results show that HIV-1 Tat expression leads to UPR/ER stress in astrocytes, which in turn contributes to astrocyte-mediated Tat neurotoxicity, and raise the possibility of developing HIV/neuroAIDS therapeutics targeted at UPR/ER stress.
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