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Cytotoxic effect on lymphocytes of Tat from human immunodeficiency virus (HIV‐1)
Author(s) -
Benjouad Abdelaziz,
Mabrouk Kamel,
Moulard Maxime,
Gluckman Jean-Claude,
Rocht Hervé,
Van Rietschoten Jurphaas,
Sabatier Jean-Marc
Publication year - 1993
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(93)80049-z
Subject(s) - cytotoxic t cell , virology , human immunodeficiency virus (hiv) , biology , immunology , in vitro , biochemistry
The human immunodeficiency virus type 1 (HIV‐1) genome codes for trans ‐activator Tat , an 86‐residue protein whose expression is critical for viral replication. Full‐length Tat and Tat peptides from HIV‐1 were chemically synthesized using optimized solid phase technique. Synthetic Tat 2 in86 , was found not only to inhibit antigen‐induced human peripheral blood lymphocyte (PBL) proliferation in vitro, as described by Viscidi et al. [1989, Science 246, 1606‐1608], but also mitogen‐induced PBL proliferation, with 50% inhibition obtained at 0.9 and 8 μ;M, respectively. To assess the mechanism by which Tat exert its inhibitory effect, we analysed its interaction and effect on CD4 + ‐cells. Direct fluorescence and indirect immunofluorescence assays analysed by flow cytometry showed that fluorescein isothiocyanate‐labeled and ‐unlabeled Tat interact (>0.2 μ;M) with CD 4 ‐expressing lymphoid cells (CEM cell line). Experiments of chromium‐51 release and Trypan blue exclusion on these tumor cells in vitro have demonstrated the capacity of Tat to modify cellular membrane permeability and cell viability, in a dose‐dependent manner. The use of Tat peptides revealed that those containing the Tat basic region from 49 to 57 were able to bind to the cell membrane and to exhibit a cytotoxic activity on lymphocytes. Together, the data suggest that the potential cytotoxicity of Tat on lymphocytes could be directly implicated in virus‐induced immune dysfunction observed in HIV‐1 infected patients.