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.
The Nef protein of HIV-1 is suggested to play a role in depletion of uninfected CD4+ T cells leading to the development of AIDS. The recombinant soluble Nef protein was shown to bind to cell surfaces of various murine lymphoid cell lines, including T and B lymphocytes, mastocytoma cells and macrophages. Cross-linking of the cell-bound Nef protein with anti-Nef antibodies induced apoptotic cytolysis of the cells. Although primary lymphocytes from young mice resisted Nef binding and Nef-induced cytolysis, treatment of the cells with concanavalin A or phytohemagglutinin made them susceptible to these activities, indicating that cellular activation is required for the apoptosis. The Nef- induced apoptosis also occurred with murine cells not expressing CD95 ( Fas). These findings were quite similar to those obtained for human blood cells, suggesting that the mouse is applicable for analysis of Nef activities. The Nef-induced apoptosis was efficiently suppressed by serine/threonine protein kinase inhibitors, H7, fasudil hydrochloride and M3, which did not inhibit CD95 (Fas)-mediated apoptosis. On the other hand, bisindolylmaleimide, a protein kinase C inhibitor which inhibits CD95 (Fas)-mediated apoptosis, did not affect Nef-induced apoptosis. These results suggest that the Nef- induced apoptosis of murine cells involved a serine/threonine protein kinase-dependent signal transduction pathway distinct from the CD95 (Fas)-mediated system.[1]References
- 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. Okada, H., Takei, R., Tashiro, M. FEBS Lett. (1997) [Pubmed]
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