Polyomavirus Large T Antigen Interact with the DISC and Protect against Fas Induced Apoptosis

. Polyomavirus (Py), a member of the papovaviruses, causes tumors in rodents. Polyomavirus large T antigen (PyLT-Ag), a nucleophosphoprotein essential for regulating viral gene expression, modulates the cell cycle by binding to the Rb tumor suppressor gene product and immortalizes primary cells in culture. As part of their lytic cycle, viruses have developed strategies and appropriate viral gene products to either induce, delay, or totally block apoptosis (1,2). The receptor of FasL, CD95/Apo1/FasR, causes oligomerization of the FasR to provoke the formation of a death-inducing signaling complex (DISC) that transmits external apoptotic signals to the cytoplasm, mitochondria, and ultimately to the nuclei (3,4). Our laboratory has previously reported that a Sertoli cell line derived from transgenic mice expressing PyLT-Ag are resistant to treatment with FasR agonist antibodies (FasR(Ab)) (5). These results suggested that the inhibition of FasR(Ab)-induced apoptosis in these cells was attributable to PyLT-Ag expression. In this study, we investigated the effect of PyLT-Ag expression in murine cell lines sensitive to FasR(Ab) treatment.