ArticleScientific reports2019
A Naturally Occurring Polymorphism in the HIV-1 Tat Basic Domain Inhibits Uptake by Bystander Cells and Leads to Reduced Neuroinflammation.
Article in Scientific reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
32 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 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
- HPV Capsid-Derived Cationic Peptides for Cargo Delivery and Antiviral Activity.bioRxiv : the preprint server for biology · 2026Article
- Interferon-induced protein IFIT3 as a molecular nexus of neuroinflammation in Alzheimer's disease and HIV-associated neurocognitive disorders.Journal of neuroinflammation · 2026Article
- Overcoming Ligand Discovery Challenges: Developing Peptide-Based Tracers for SPSB2.ACS chemical biology · 2026Article
- Article
- Neuroinflammatory and Neurodegenerative Roles of HIV-1 Tat: A Review of Recent Evidence.Advances in experimental medicine and biology · 2026Review
- Beyond Viral Assembly: The Emerging Role of HIV-1 p17 in Vascular Inflammation and Endothelial Dysfunction.International journal of molecular sciences · 2025Review
- SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes.Life science alliance · 2025Article
- Impact of Phylogenetic Method Choice on Indel Analyses in HIV-1 Subtype B.Genome biology and evolution · 2025Article
- Retrospective Observational Study of CSF-Derived HIV-1 Tat and Vpr Amino Acid Sequences in a South African Pediatric Cohort with HIV Subtype C.International journal of molecular sciences · 2025Observational
- Neurovirulent and non-neurovirulent strains of HIV-1 and their Tat proteins induce differential cytokine-chemokine profiles.NeuroImmune pharmacology and therapeutics · 2025Article
- HIV Tat as a latency reversing agent: turning the tables on viral persistence.Frontiers in immunology · 2025Review
- HIV-1 Tat-induced disruption of epithelial junctions and epithelial-mesenchymal transition of oral and genital epithelial cells lead to increased invasiveness of neoplastic cells and the spread of herpes simplex virus and cytomegalovirus.Frontiers in immunology · 2025Review
- Transactivator of Transcription (Tat)-Induced Neuroinflammation as a Key Pathway in Neuronal Dysfunction: A Scoping Review.Molecular neurobiology · 2024Article
- The association between HIV-1 Tat and Vif amino acid sequence variation, inflammation and Trp-Kyn metabolism: an exploratory investigation.BMC infectious diseases · 2024Article
- Impact of subtype C-specific amino acid variants on HIV-1 Tat-TAR interaction: insights from molecular modelling and dynamics.Virology journal · 2024Article
- Rev Protein Diversity in HIV-1 Group M Clades.Viruses · 2024Article
- Bioinformatics Insights on Viral Gene Expression Transactivation: From HIV-1 to SARS-CoV-2.International journal of molecular sciences · 2024Article
- Role of HIV-1 Tat Protein Interactions with Host Receptors in HIV Infection and Pathogenesis.International journal of molecular sciences · 2024Review
- HIV-1 Tat commandeers nuclear export of Rev-viral RNA complex by controlling hnRNPA2-mediated splicing.Journal of virology · 2023Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
HIV-1 Tat protein contributes to HIV-neuropathogenesis in several ways including its ability to be taken up by uninfected bystander CNS cells and to activate inflammatory host genes causing synaptic injury. Here, we report that in the globally dominant HIV-1 clade C, Tat displays a naturally occurring polymorphism, R57S, in its basic domain, which mediates cellular uptake. We examined the effect of this polymorphism on Tat uptake and its consequences for cellular gene transactivation. In decapeptides corresponding to the basic domain, a R57S substitution caused up to a 70% reduction in uptake. We also used a transcellular Tat transactivation assay, where we expressed Tat proteins of HIV-1 clade B (Tat-B) or C (Tat-C) or their position 57 variants in HeLa cells. We quantified the secreted Tat proteins and measured their uptake by TZM-bl cells, which provide readout via an HIV-1 Tat-responsive luciferase gene. Transactivation by Tat-B was significantly reduced by R57S substitution, while that of Tat-C was enhanced by the reciprocal S57R substitution. Finally, we exposed microglia to Tat variants and found that R57 is required for maximal neuroinflammation. The R57S substitution dampened this response. Thus, genetic variations can modulate the ability of HIV-1 Tat to systemically disseminate neuroinflammation.
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Registered trials
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