Human immunodeficiency virus type 1 Nef protein on the cell surface is cytocidal for human CD4+ T cells

Nef protein of HIV‐1 induces apoptotic cytolysis of murine lymphoid cells independently of CD95 (Fas) and its suppression by serine/threonine protein kinase inhibitors

“…These results appear quite similar to those obtained for human blood cells [8]. Although mice are insusceptible to HIV-1 infections, the present study suggests that the murine model is useful for investigating the Nef-induced apoptotic cytolysis of uninfected bystander cells [5][6][7][8], which may be responsible in part for the extensive destruction of a variety of blood cells during the course of HIV-1 infection [1][2][3][4], and to test drugs inhibiting the Nef-mediated apoptosis to prevent the development of AIDS. The Nef-induced apoptotic cytolysis of murine cells was efficiently inhibited by serine/threonine PK inhibitors, fasudil hydrochloride, its metabolite M3 [10][11][12], and H7.…”

Macrophages and HIV-1: dangerous liaisons

“…Hence, Nef could promote T cell infection by activating signals on antigen-presenting cells that activate resting T lymphocytes in lymphoid organs (Swingler et al, 2003). Although most studies mainly concerned endogenously expressed Nef, some recent reports suggested that exogenous Nef, which is found in the serum of AIDS patients at ng levels (Fujii et al, 1996), also contributes to macrophage activation. Exogenous Nef can be internalised by macrophages.…”

Constitutive Activation of Phosphatidylinositol 3-Kinase Signaling Pathway Down-regulates TLR4-mediated Tumor Necrosis Factor-α Release in Alveolar Macrophages from Asymptomatic HIV-positive Persons in Vitro

“…Macrophages-HIV Nef protein was detected in the serum of HIV-infected subjects in the range of 5-10 ng/ml (29), and antibodies directed against Nef have been found in a large proportion of infected subjects (30). Exogenous Nef has been found to enter cells by adsorptive endocytosis after nonspecific binding to the surface of CD4 T-cells, primary macrophages, and U937 cells and to activate the signaling pathway such as STAT-1 in human monocyte macrophages (31).…”