ArticleThe Journal of biological chemistry2009
Mechanism for HIV-1 Tat insertion into the endosome membrane.
Article in The Journal of biological chemistry, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 54 citations in OpenAlex.
- pH-responsive in situ antigen capture and cytosolic delivery synergize to elicit robust systemic antitumor immunity.Journal of nanobiotechnology · 2026Article
- HIV-1 Tat favors the multiplication of Mycobacterium tuberculosis and Toxoplasma by inhibiting clathrin-mediated endocytosis and autophagy.PLoS pathogens · 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
- HIV Tat as a latency reversing agent: turning the tables on viral persistence.Frontiers in immunology · 2025Review
- 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
- Structural Insights into the Mechanism of HIV-1 Tat Secretion from the Plasma Membrane.Journal of molecular biology · 2023Article
- Article
- The impact of Gag non-cleavage site mutations on HIV-1 viral fitness from integrative modelling and simulations.Computational and structural biotechnology journal · 2021Article
- Skipped Over: Tuning Natural Killer Cells Toward HIV Through Alternative Splicing.AIDS research and human retroviruses · 2020Article
- Morphine exposure exacerbates HIV-1 Tat driven changes to neuroinflammatory factors in cultured astrocytes.PloS one · 2020Article
- HIV-1 Tat Length: Comparative and Functional Considerations.Frontiers in microbiology · 2020Article
- HIV and Alzheimer's disease: complex interactions of HIV-Tat with amyloid β peptide and Tau protein.Journal of neurovirology · 2019Review
- Genetic variation and function of the HIV-1 Tat protein.Medical microbiology and immunology · 2019Review
- Article
- Cyclophilin A enables specific HIV-1 Tat palmitoylation and accumulation in uninfected cells.Nature communications · 2018Article
- Defining the molecular mechanisms of HIV-1 Tat secretion: PtdIns(4,5)PTraffic (Copenhagen, Denmark) · 2018Review
- Initial Evaluation of Antibody-conjugates Modified with Viral-derived Peptides for Increasing Cellular Accumulation and Improving Tumor Targeting.Journal of visualized experiments : JoVE · 2018Article
- Design of aromatic-containing cell-penetrating peptide mimics with structurally modified π electronics.Chemistry (Weinheim an der Bergstrasse, Germany) · 2015Article
- IL-7 receptor recovery on CD8 T-cells isolated from HIV+ patients is inhibited by the HIV Tat protein.PloS one · 2014Article
- Expression of human endogenous retrovirus type K (HML-2) is activated by the Tat protein of HIV-1.Journal of virology · 2012Article
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The human immunodeficiency virus, type 1, transactivating protein Tat is a small protein that is strictly required for viral transcription and multiplication within infected cells. The infected cells actively secrete Tat using an unconventional secretion pathway. Extracellular Tat can affect different cell types and induce severe cell dysfunctions ranging from cell activation to cell death. To elicit most cell responses, Tat needs to reach the cell cytosol. To this end, Tat is endocytosed, and low endosomal pH will then trigger Tat translocation to the cytosol. Although this translocation step is critical for Tat cytosolic delivery, how Tat could interact with the endosome membrane is unknown, and the key residues involved in this interaction require identification. We found that, upon acidification below pH 6.0 (i.e. within the endosomal pH range), Tat inserts into model membranes such as monolayers or lipid vesicles. This insertion process relies on Tat single Trp, Trp-11, which is not needed for transactivation and could be replaced by another aromatic residue for membrane insertion. Nevertheless, Trp-11 is strictly required for translocation. Tat conformational changes induced by low pH involve a sensor made of its first acidic residue (Glu/Asp-2) and the end of its basic domain (residues 55-57). Mutation of one of these elements results in membrane insertion above pH 6.5. Tat basic domain is also required for efficient Tat endocytosis and membrane insertion. Together with the strict conservation of Tat Trp among different virus isolates, our results point to an important role for Tat-membrane interaction in the multiplication of human immunodeficiency virus type 1.
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