Cytotoxic effect on lymphocytes of Tat from human immunodeficiency virus (HIV‐1)

FEBS Letters

Van Rietschoten, Jurphaas²  Mabrouk, Kamel²  Moulard, Maxime²  Rocht, Hervé²  Benjouad, Abdelaziz²  Sabatier, Jean-Marc²  Gluckman, Jean-Claude¹ 

[1] CERVI, CNRS URA 1463. Hôpital de la Pitié Salpêtrière, Bd de l'hôpital, 75651-Paris Cédex 13, France;Laboratoire de Biochimie, CNRS URA 1455, Faculté de Médecine Secteur Nord, BdP. Dramard, 13916-Marseille Cédex 20, France

关键词: HIV;    Tat;    Cytotoxicity;    Lymphocyte;    Synthetic peptide;   

DOI  :  10.1016/0014-5793(93)80049-Z

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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 CD₄-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.

【 授权许可】

Unknown