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

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.