Thus the mechanism of protection by VLPs against AKI is based on activation of both pathways leading to survival. Chaperons were recently implicated in renal protection against AKI. Akt-1 is a key player in activation of survival pathway, leading to apoptosis arrest. Akt-1 was also shown to diminish oxidative stress. Our experiments in cultured mouse tubular cells indicate that part of the apoptotic arrest is mediated via the inhibition of capspase 9 and caspase 3. Our ongoing studies in cultured monkey kidney cells, using proteomics arrays, have indicated that VLPs activate PLCc. Using specific inhibitors we found that Akt-1 activation fully depends on PLC-signaling, and only partly on PI3K. Activation of Akt-1 by phosphrylation at serine 473 was shown to lead to survival pathway via regulation of proapoptotic proteins such as Bad, caspase 9 and p53. Furthermore, a number of publications showed that activation of PLC-PI3K-AKT signaling led to apoptosis arrest in neurodegeneration and atherosclerosis. We propose that a similar pathway is induced by the SV40 VLPs in the kidney. Our unpublished studies further indicate that PLCc signaling leads to upregulation of Hsp/c70. BI-D1870 Induction of Hsp/c70 might proceed via PLC dependent PKC activation as previously described for a heat stress model. Chaperones play a role in SV40 disassembly. Here we show that the infecting virus induces chaperone upregulation via signals triggered by its coat proteins, very early post infection. Taken together, these findings suggest that upregulation of cellular chaperone may be part of the signaling program that functions in viral entry and disassembly. We have asked whether VLPs may also have a therapeutic effect for animals with AKI. The experiments indicated that administration of VLPs following the HgCl2 insult did not lead to increased survival. This is most likely because of the time required for the induction of the Akt survival pathway and chaperone upregulation. Thus, the VLPs do not appear to lead to kidney regeneration, but rather to prevention of injury. A critical limitation in treating human patients with a foreign protein such as SV40 VLPs is the risk of developing immune response, which would preclude repeated administrations. We and others found that SV40 vectors used for gene delivery in mice did not elicit neither cellular immune response nor NVP-BKM120 PI3K inhibitor humoral immune response. This may be partly due to the unique mode of entry of SV40 via caveolae and the ER, bypassing the endosomal pathway. In addition, we found that SV40 activates FLIP, via phosphorylation, following infection of tissue-cultured cells. FLIP was demonstrated to suppresses downstream signals from T killer cells and could therefore also partly account for non-immunogenicity of SV40 vectors.