The DOI matches its Crossref record; 64 of the 64 references it cites were found in a registry or an index.
HIV-1 Tat Alters Neuronal Autophagy by Modulating Autophagosome Fusion to the Lysosome: Implications for HIV-Associated Neurocognitive Disorders
Open accessAbstract
Antiretroviral therapy has increased the life span of HIV+ individuals; however, HIV-associated neurocognitive disorder (HAND) occurrence is increasing in aging HIV patients. Previous studies suggest HIV infection alters autophagy function in the aging CNS and HIV-1 proteins affect autophagy in monocyte-derived cells. Despite these findings, the mechanisms leading to dysregulated autophagy in the CNS remain unclear. Here we sought to determine how HIV Tat dysregulates autophagy in neurons. Tat caused a dose-dependent decrease in autophagosome markers, microtubule-associated protein-1 light chain β II (LC3II), and sequestosome 1(SQSTM1), in a membrane-enriched fraction, suggesting Tat increases autophagic degradation. Bafilomycin A1 increased autophagosome number, LC3II, and SQSTM1 accumulation; Tat cotreatment diminished this effect. Tat had no effect when 3-methyladenine or knockdown of beclin 1 blocked early stages of autophagy. Tat increased numbers of LC3 puncta and resulted in the formation of abnormal autophagosomes in vitro. Likewise, in vivo studies in GFAP-Tat tg mice showed increased autophagosome accumulation in neurons, altered LC3II levels, and neurodegeneration. These effects were reversed by rapamycin treatment. Tat colocalized with autophagosome and lysosomal markers and enhanced the colocalization of autophagosome with lysosome markers. Furthermore, co-IP studies showed that Tat interacts with lysosomal-associated membrane protein 2A (LAMP2A) in vitro and in vivo, and LAMP2A overexpression reduces Tat-induced neurotoxicity. Hence, Tat protein may induce autophagosome and lysosome fusion through interaction with LAMP2A leading to abnormal neuronal autophagy function and dysregulated degradation of critical intracellular components. Therapies targeting Tat-mediated autophagy alterations may decrease neurodegeneration in aging patients with HAND.
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“HIV-TAT can damage lysosome function in microglia and in neuron [46, 75].”
From HIV-TAT dysregulates microglial lipid metabolism through SREBP2/miR-124 axis: Implication of lipid droplet accumulation microglia in NeuroHIV (2025) · cites this paper as [75]
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1 retracted
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Cited by
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Items 101–133 of 133
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TLR7 Mediates HIV ‐1 Tat‐Induced Cellular Senescence in Human Astrocytes
Rezagholizadeh, N., Datta, G., Hasler, W. A., Nguon, E. C., Smokey, E. V., & Chen, X. (2025) · Aging Cell · doi:10.1111/acel.70086 · Cited by 3
“…factors induce endolysosome dysfunction including gp120 (Bae et al. 2014; Datta et al. 2019; Halcrow et al. 2022), Tat (Chen et al. 2013; Fields et al. 2015; Hui et al. 2012), ART drugs (Hui et al. 2021; Tripathi et al. 2019), methamphetamine (Cubells et al. 1994; Talloczy et al. 2008),…”
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Du, C., Li, G., & Han, G. (2023) · Biosafety and Health · doi:10.1016/j.bsheal.2023.04.002 · Cited by 3
“The neuro-toxic proteins tat and gp120 produced by infected cells can directly impair neuronal signals transmission and synaptic plasticity, affect neuronal autophagy and induce neuronal apoptosis [43 – 46].”
The role of immunometabolism in HIV-associated depression and cognitive impairment
Andalibi, M. S. S., & Ellis, R. J. (2024) · Elsevier eBooks · doi:10.1016/b978-0-323-99744-7.00028-6 · Cited by 3
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“Our previous works in postmortem brain specimens from PWH illustrate alterations in metabolic pathways, including mitochondrial dynamics, biogenesis, and autophagic flux [18,19].”
Self-citationJia, X.-X., Shao, Q., Chaudhry, A. R., Kinlock, B. L., Izban, M. G., Zhang, H.-Y., Villalta, F., Hildreth, J. E. K., & Liu, B. (2021) · Pathogens · doi:10.3390/pathogens10091192 · Cited by 2
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“However, Tat can counteract this degradation by decreasing the quantity of the autophagy markers LC3II andp62/SQSTM1 coupled with the membrane in neurons [199].”
BackgroundHIV‐1, Drug Addiction, and Autophagy
Guo, M., Periyasamy, P., & Buch, S. J. (2016) · InTech eBooks · doi:10.5772/63980
“also demonstrated that TAT altered neuronal autophagy by modulating autophagosome fusion to the lysosome [27].”
BackgroundHIV Tat and Morphine-induced Neurodegeneration in a Beclin 1 Hemizygous Mouse Model
Lapierre, J. (2018) · FIU - Digital Commons (Florida International University) · doi:10.25148/etd.fidc007019
“Studies have shown that the effects of Tat on autophagy are largely dependent on conditions, concentration, and cell type, either activating or suppressing autophagy function in glial cells or neurons [191, 193, 298].”
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Self-citationHIV Exacerbates Atherosclerosis by Altering Macrophage Function
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Réplication et séquestration du VIH-1 dans les macrophages
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Regulation of the Akt/mTORC1 Pathway by HIV Transcriptional Activator Tat in B Cells
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Song, B., Liu, C., Hu, J., Zhao, X., Fan, H., Liu, T., Gao, G., Zhang, X., Guang, X., Zhou, Q., et al. (2026) · Autophagy · doi:10.1080/15548627.2026.2669987
“For instance, the HIV-1 Tat protein has been identified to influence neuronal autophagy by modulating the fusion of autophagosomes with lysosomes, a mechanism closely associated with HIV-associated neuro-cognitive disorders [38].”
Williams, M. E., & Eugenín, E. A. (2026) · NeuroImmune Pharmacology and Therapeutics · doi:10.1515/nipt-2026-0017
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“…ALN, but other viral proteins may also be implicated, like the accessory protein and virulence factor, nef, and the envelope protein, gp120 (Ditatkovski et al., 2020; Fields et al., 2015, Guo and Buch, 2019; Hategan et al., 2019; Leymarie et al., 2017; Thompson et al., 2024; Scuderi et al., 2025).”
Xia, C., Fan, X., Cheng, F., Yang, S., Zhang, X., & Chen, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1990644
Metadata
- Authors
- Fields, J., Dumaop, W., Elueteri, S., Campos, S., Serger, E., Trejo, M., Kosberg, K., Adame, A., Spencer, B., Rockenstein, E., He, J. J., & Masliah, E.
- Affiliations
- University of California San Diego (US)
- University of North Texas Health Science Center (US)
- Venue
- The Journal of Neuroscience
- Publisher
- Society for Neuroscience
- Published
- 2015-02-04
- Volume
- 35
- Issue
- 5
- Pages
- 1921-1938
- ISSN
- 0270-6474 (ISSN-L)
- 1529-2401
- PMC
- PMC4315828
- OpenAlex
- W2050541584
- Cited by
- 133
- References
- 64
- Citations by year
- 2026: 6 · 2025: 7 · 2024: 11 · 2023: 6 · 2022: 12 · 2021: 14 · 2020: 21 · 2019: 15 · 2018: 15 · 2017: 13 · 2016: 9 · 2015: 4
- FWCI
- 10.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute on Aging (AG043384, R01AG043384)
- National Institute of Mental Health (U01MH083506, R01MH062962, U24MH100928, U01MH083500, MH5974, MH83506, MH062962, U24MH100929)
- National Institute of Neurological Disorders and Stroke (F32NS083426)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Autophagy in Disease and Therapy
- Life Sciences › Immunology and Microbiology › Virology › HIV Research and Treatment
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Keywords
- HIV-1 Tat protein, neuronal autophagy, autophagosome-lysosome fusion, HIV-associated neurocognitive disorders, neurodegeneration, LAMP2A, LC3-II, p62, bafilomycin A1, rapamycin, neurotoxicity
- MeSH terms
- Animals, Autophagy, Cells, Cultured, Lysosomes, Neurons, Phagosomes, Protein Binding, HIV-1, AIDS Dementia Complex, Cell Line, Tumor, Mice, Rats, Lysosomal-Associated Membrane Protein 2, tat Gene Products, Human Immunodeficiency Virus
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