HIV-1 Tat protects CD4+ Jurkat T lymphoblastoid cells from apoptosis mediated by TNF-related apoptosis-inducing ligand.
We have here investigated the effect of TNF-related apoptosis-inducing ligand (TRAIL), a new member of the TNF cytokine superfamily, on the survival of Jurkat lymphoblastoid cell lines stably transfected with plasmids expressing the wild-type or mutated (Cys22) human immunodeficiency virus type 1 (HIV-1) tat gene. Jurkat cells transfected with wild-type tat were resistant to TRAIL-mediated apoptosis, while Jurkat cells mock-transfected with the control plasmid or with a mutated nonfunctional tat cDNA were highly susceptible to TRAIL-mediated apoptosis. Also, pretreatment with low concentrations (10-100 ng/ml) of extracellular synthetic Tat protein partially protected Jurkat cells from TRAIL-mediated apoptosis. Taken together, these results demonstrated that endogenously expressed tat and, to a lesser extent, extracellular Tat block TRAIL-mediated apoptosis. Since it has been shown that primary lymphoid T cells purified from HIV-1-infected individuals are more susceptible than those purified from normal individuals to TRAIL-mediated apoptosis, our findings underscore a potentially important role of Tat in protecting HIV-1-infected cells from TRAIL-mediated apoptosis.
Microbiology Section, Department of Clinical and Experimental Medicine, University of Bologna, Via Massarenti 9, Bologna, 40138, Italy.
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Maldini
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Celeghini
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La Placa
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D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D015696:Gene Products, tat / Q000502:physiology*; D015497:HIV-1 / Q000502:physiology*; D006801:Humans; D020287:In Situ Nick-End Labeling; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000502:physiology*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor / Q000032:analysis; D053221:TNF-Related Apoptosis-Inducing Ligand; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D054322:tat Gene Products, Human Immunodeficiency Virus
D051017:Apoptosis Regulatory Proteins; D015696:Gene Products, tat; D008562:Membrane Glycoproteins; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505639:TNFRSF10B protein, human; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; D054322:tat Gene Products, Human Immunodeficiency Virus