HIV-1 Tat-driven Glutamate Dysregulation: Implications for Cognitive Impairment in HAND

Brenna C Duffy; Michael R Nonnemacher; Sandhya Kortagere

doi:10.1007/s11904-026-00789-w

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HIV-1 Tat-driven Glutamate Dysregulation: Implications for Cognitive Impairment in HAND

Journal article

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HIV-1 Tat-driven Glutamate Dysregulation: Implications for Cognitive Impairment in HAND

Brenna C Duffy, Michael R Nonnemacher and Sandhya Kortagere

Current HIV/AIDS reports, v 23(1), 18

15 Jun 2026

DOI: https://doi.org/10.1007/s11904-026-00789-w

PMID: 42295509

Featured in Collection : Research Supported by Drexel Libraries' OA Programs

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Abstract

AIDS Dementia Complex - metabolism

Animals

Astrocytes - metabolism

Astrocytes - virology

Glutamic Acid - metabolism

HIV Infections - complications

HIV-1 - metabolism

Humans

Microglia - metabolism

Microglia - virology

tat Gene Products, Human Immunodeficiency Virus - metabolism

HIV-1-associated neurocognitive disorders (HAND) manifest in 15% to 50% of people with HIV, impairing learning and memory and executive function. The chronic generation of HIV-1 Transactivator of transcription (Tat) likely contributes to HAND via direct neuronal toxicity and glial-mediated toxicity. This review summarizes our current understanding of how chronic Tat generation from microglia and astrocytes promote glutamate excitotoxicity. In recent years, the indirect effects of Tat through the activation of glial cells have gained significant interest. This review highlights microglia and astrocytes as HIV-1 reservoirs that release Tat protein in the central nervous system. Specific context is provided on the Tat isoforms and models in the recent literature and their impact on our understanding of the neuronal and glial-mediated effects of Tat on glutamate transmission. Transgenic and transduction models of HIV-1 Tat expression in glia have demonstrated Tat-induced glial activation phenotypes that contribute to dysregulation of glutamate receptors and transporters. Investigating both glial-mediated and direct mechanisms of Tat-potentiated excitotoxicity can identify therapeutic targets that are relevant for HAND.

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Title: HIV-1 Tat-driven Glutamate Dysregulation: Implications for Cognitive Impairment in HAND
Creators: Brenna C Duffy - Drexel University
Michael R Nonnemacher - Thomas Jefferson University
Sandhya Kortagere (Corresponding Author) - Drexel University
Publication Details: Current HIV/AIDS reports, v 23(1), 18
Publisher: Springer Nature
Grants: HIV-1 Tat genetic variation impacts NeuroAIDS, 5R01NS089435, National Institutes of Health (United States, Bethesda) - NIH
Grant note: NIH-1F31MH139360-01A1 / NIH HHS
Resource Type: Journal article
Language: English
Academic Unit: Microbiology and Immunology
Web of Science ID: WOS:001793370000001
Other Identifier: 991022191263504721

HIV-1 Tat-driven Glutamate Dysregulation: Implications for Cognitive Impairment in HAND

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