Many viruses are known to disarm or suppress the cell death machinery of infected cells. Apoptotic cell death can be activated by aggregation of the CD95 cell surface death receptor in sensitive cells, and in most insensitive cells treated with sensitizing agents such as interferon-gamma or inhibitors of protein synthesis. We show that, subsequent to sequestration and inactivation of the p53 tumour suppressor protein, SV40 abrogates p53-dependent, DNA damage-inducible up-regulation of CD95 surface expression. Loss of surface up-regulation of CD95 after sub-lethal mitomycin C treatment resulted in an impaired enhancement of both caspase-8 cleavage and apoptotic cell death following CD95 aggregation. We conclude that infection of human cells with SV40 virus strongly inhibits DNA damage-induced enhancement of CD95-mediated apoptosis.

Laboratory of Apoptosis Research Masaryk Memorial Cancer Institute Zluty Kopec 7 656 53 Brno The Czech Republic

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