HIV-1 Nef protein-induced apoptotic cytolysis of a broad spectrum of uninfected human blood cells independently of CD95(Fas)

• Published in: FEBS letters 1997-09, Vol.414 (3), p.603-606
• Main Authors: Okada, Harue, Takei, Ryoichi, Tashiro, Masato
• Format: Article
• Language: English
• Subjects: AIDS; AIDS/HIV; Apoptosis; Apoptosis - drug effects; Blood Cells - drug effects; Blood Cells - metabolism; CD4-Positive T-Lymphocytes - metabolism; CD8-Positive T-Lymphocytes - metabolism; Cytotoxicity; fas Receptor - metabolism; Gene Products, nef - metabolism; Gene Products, nef - pharmacology; HIV-1; HIV-1 - chemistry; Humans; Nef; nef Gene Products, Human Immunodeficiency Virus
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(97)01080-6

The Nef protein of HIV-1 binds to uninfected CD4 +T lymphocytes and induces apoptotic cytolysis of the cells. We examined several human blood cell lines and peripheral blood mononuclear cells (PBMCs) for Nef-induced apoptotic cell death. Soluble Nef protein was shown to bind to the cell surface of not only CD4 +T cells but also CD8 +T lymphocytes, B lymphocytes, macrophages and neutrophils. PBMCs from normal subjects resisted Nef binding, and activation of the cells with phytohemagglutinin or concanavalin A converted the cells to be susceptible to the binding. Cross-linking of the Nef proteins bound to the cell surfaces with anti-Nef antibody-induced apoptotic cytolysis of the cells. The Nef-mediated apoptosis occurred independently of CD95(Fas). These results suggest that soluble Nef protein, which is found in sera of HIV-1 infected patients, is involved in the destruction of a broad spectrum of uninfected blood cells leading to immune suppression.