ArticleMolecular biology of the cell2004
HIV-1 Tat enters T cells using coated pits before translocating from acidified endosomes and eliciting biological responses.
Article in Molecular biology of the cell, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 88 papers.
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Who cites it
88 citing papers in PubMed, 201 citations in OpenAlex.
- scRNA sequencing revealed HIV-associated inflammation-mediated lung epithelial dysregulation and fibroblast remodeling.Frontiers in immunology · 2026Article
- A multistep platform identifies spleen-tropic lipid nanoparticles for in vivo T cell-targeted delivery of gene-editing proteins.Science advances · 2025Article
- HIV-1 Tat favors the multiplication of Mycobacterium tuberculosis and Toxoplasma by inhibiting clathrin-mediated endocytosis and autophagy.PLoS pathogens · 2025Article
- SLC38A9 is directly involved in Tat-induced endolysosome dysfunction and senescence in astrocytes.Life science alliance · 2025Article
- Novel Nucleus-Oriented Quenched Activity-Based Probes Link Cathepsin Nuclear Localization with Mitosis.ACS sensors · 2025Article
- Genotoxic consequences of viral infections.Npj viruses · 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
- Comparing Cell Penetration of Biotherapeutics across Human Cell Lines.ACS chemical biology · 2024Article
- HIV-1 Tat Induces Dysregulation of PGC1-Alpha and Sirtuin 3 Expression in Neurons: The Role of Mitochondrial Biogenesis in HIV-Associated Neurocognitive Disorder (HAND).International journal of molecular sciences · 2023Article
- Features of Tat Protein in HIV-1 Sub-Subtype A6 Variants Circulating in the Moscow Region, Russia.Viruses · 2023Article
- A Tripartite Complex HIV-1 Tat-Cyclophilin A-Capsid Protein Enables Tat Encapsidation That Is Required for HIV-1 Infectivity.Journal of virology · 2023Article
- Article
- TGF-β Inhibitors for Therapeutic Management of Kidney Fibrosis.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Long noncoding RNAs (lncRNAs) in HIV-mediated carcinogenesis: Role in cell homeostasis, cell survival processes and drug resistance.Non-coding RNA research · 2022Review
- The ins and outs of virus trafficking through acidic CaCell calcium · 2022Review
- HIV-1 Tat endocytosis and retention in endolysosomes affects HIV-1 Tat-induced LTR transactivation in astrocytes.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Sirtuins Modulation: A Promising Strategy for HIV-Associated Neurocognitive Impairments.International journal of molecular sciences · 2022Review
- Endolysosome iron restricts Tat-mediated HIV-1 LTR transactivation by increasing HIV-1 Tat oligomerization and β-catenin expression.Journal of neurovirology · 2021Article
- Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment.Frontiers in immunology · 2021Review
- RETRACTED: Optimized Conjugation of Fluvastatin to HIV-1 TAT Displays Enhanced Pro-Apoptotic Activity in HepG2 Cells.International journal of molecular sciences · 2020Article
28 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The HIV-1 Tat protein is secreted by infected cells. Extracellular Tat can affect bystander uninfected T cells and induce numerous biological responses such as apoptosis and cytokine secretion. Tat is likely involved in several immune disorders during AIDS. Nevertheless, it is not known whether Tat triggers cell responses directly upon binding to signaling receptors at the plasma membrane or after delivery to the cytosol. The pathway that enables Tat to reach the cytosol is also unclear. Here we visualized Tat within T-cell-coated pits and endosomes. Moreover, inhibitors of clathrin/AP-2-mediated uptake such as chlorpromazine, activated RhoA, or dominant-negative mutants of Eps15, intersectin, dynamin, or rab5 impaired Tat delivery to the cytosol by preventing its endocytosis. Molecules neutralizing low endosomal pH or Hsp90 inhibitors abolished Tat entry at a later stage by blocking its endosomal translocation, as directly shown using a cell-free translocation assay. Finally, endosomal pH neutralization prevented Tat from inducing T-cell responses such as NF-kappaB activation, apoptosis, and interleukin secretion, indicating that cytosolic delivery is required for Tat signaling. Hence, Tat enters T cells essentially like diphtheria toxin, using clathrin-mediated endocytosis before low-pH-induced and Hsp90-assisted endosomal translocation. Cell responses are then induced from the cytosol.
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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.