In vitro cytocidal effects of human immunodeficiency virus type 1 Nef on unprimed human CD4+ T cells without MHC restriction

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

“…In addition to CD4+ T cells, CD8+ T cells and neutrophils, which are not infected by HIV-1, are also destroyed during the course of HIV-1 infection [2][3][4]. The Nef protein of HIV-1, found as a soluble form in sera of HIV-1-infected patients and also expressed on the surface of HIV-1-infected cells, is shown in vitro to bind to uninfected CD4+ T cells and, upon cross-linking by anti-Nef antibodies, it induces apoptotic cytolysis of the cells [5][6][7]. We have recently shown that a broad spectrum of human blood cells are also susceptible to Nef-induced apoptotic cytolysis, which occurs independently of CD95 (Fas) and requires cellular activation [8].…”

Upregulation of the Apoptosis-Associated Protein Grb3-3 in HIV-1-Infected Human CD4+ Lymphocytes

“…In addition, although Tat and Nef have been reported by other investigators to induce apoptosis (31)(32)(33)(34), it is premature to conclude that these two viral proteins cause apoptosis only through Grb3-3. Apoptosis involves numerous cellular factors participating in a variety of signaling pathways and as a result, different stimuli can cause cell death via distinct pathways (35)(36)(37).…”

Expression of HIV-1 <i>nef</i> in Yeast Causes Membrane Perturbation and Release of the Myristylated Nef Protein

“…While occasional labelling concentrated in patches at the cell membrane is observed (data not shown), its infrequent appearance suggests that it might be an artefact. Nef expressed from a baculovirus expression system and from T cells acutely and persistently infected with HIV-1 was found clustered at the cell surface as well as within the cytoplasm [15,16], and insect cells decorated with Nef on their surface could kill bystander cells [17]. Peculiarities in the surface of a yeast cell may contribute to our difficulty to detect Nef on the cell surface or it may be released from the yeast very rapidly.…”

“…These properties of Nef have been suggested from previous studies with myristylated peptides [9,10,36], however, this appears to be the first demonstration of an effect from the myristylated Nef protein on cellular membranes. It is of interest that Fujii et al [17] have indicated that cell surface Nef could kill bystander cells [17], however, the mechanism by which this occurred was not described. In view of this and our data here, we suggest that Nef, like other extracellular HIV-1 proteins Tat, Vpr and gp120, should be also considered as a candidate for extracellular effects, including bystander killing in AIDS.…”