ENA0000GenomicsMultiomicsBioinformatics Section, DIR IT & Bioinformatics, NINDS/NIHhttps://www.ebi.ac.uk/ena/browser/view/PRJNA190028Homo sapiensAnti-retroviral therapy (ART) has transformed human immunodeficiency virus (HIV) infection from a fatal illness to a chronic condition by controlling viral replication and restoring immune function. However, chronic T-cell activation can be observed in 20-35% of individuals on ART, resulting in an immune reconstitution inflammatory syndrome (IRIS) [1-3]. IRIS involving the CNS can result in permanent disability and death [4]. Tat is a viral protein produced in HIV-infected cells and released into the extracellular space [5]. We show that the secreted-Tat protein activated uninfected T-cells in an antigen-independent manner without inducing proliferation. Notably, Tat induced the secretion of IL-17 from T-cells and increased the percentage of T-cells with a Th17 phenotype. T-cell activation was independent of the T-cell receptor but dependent on endocytosis of Tat and activation of vascular endothelial growth factor receptor 2 (VEGFR2). Tat induced global changes in histone acetylation and increased HIV infection in non-replicating T-cells. Furthermore, in an individual with CNS IRIS, Tat expressing infiltrates and secretion of IL-17 was detected in the absence of viral replication in the brain. Thus Tat can induce T-cell activation in a paracrine and autocrine manner resulting in propagation of inflammation and increased virulence. Overall design: 12 Human samples in 6 pairs: 6 Human T cell HIV tat exposed 0hrs, 6 Human T cell HIV tat exposed 24hrsENACytotoxic T-lymphocyte-associated antigen 8, Human T-Cell Lymphotropic Virus Type III, Human Immunodeficiency Virus, CTLA8, Alpha-TAT, TAT, c6orf134, Human T Lymphotropic Virus Type III, Flk 1 Receptor Tyrosine Kinase, VEGF Receptor KDR, Il17, protein complex, interleukin-17 receptor ligand, Alpha-TAT1, AIDS Virus, HTLV-III, protein, KDR Tyrosine Kinase, Ctla-8, KDR, protein-containing complex, Cell, Human Immunodeficiency, mec17, Human, Lymphadenopathy Associated Virus, protein polypeptide chains, Flk-1, native protein, Kinase Insert Domain Receptor, AIDS, natural protein, polypeptide chain, IL17, Immunodeficiency Virus, Protein, Virus, 2610110G12Rik, IL-17, Human T-Cell Leukemia Virus Type III, protein aggregate, AIDS virus, Flk-1 Protein, 0610011P08Rik, 3110080J08Rik, Acquired Immune Deficiency Syndrome Virus, Human T-Lymphotropic Virus Type III, CTLA-8, Lymphadenopathy-Associated, Viruses, AIDS Viruses, Fetal Liver Kinase 1, MEC17, Flk 1 Protein, Ctla8, Immunodeficiency Viruses, VEGF Receptor Flk 1., proteins, Human T Cell Leukemia Virus Type III, Flk-1 Receptor Tyrosine Kinase, LAV-HTLV-III, Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2, Acetyltransferase mec-17 homolog, IL-17A, Nbla00487, Fetal Liver Kinase-1, Acquired Immunodeficiency Syndrome Virus, VEGF Receptor Flk-1, Lymphadenopathy-Associated Viruses, VEGF Receptor, HIV, 2610008K08Rik, VEGFR-2, Human Immunodeficiency Viruses, Human T Cell Lymphotropic Virus Type III, C6orf134, Mec17, 2.3.1.108, Lymphadenopathy-Associated Virushuman being, human., man0.00.00.00.00.00falseHomo sapiensInduction of IL-17+ T-cells by HIV-Tat protein is mediated via Vascular Endothelial Growth Factor Receptor-22022-05-122014-02-11PRJNA190028GSE44460238982089606