Additional risk factors for HC include donor origin, NCCR (non-coding control region) viral mutants,

treatment with anti-thymocyte globulins and type of conditioning. All these factors may influence the response to adjuvant therapies. It has been shown that CDV does not affect early steps of PyV replication such as receptor binding and entry (Bernhoff et al., 2008). Neither initial transcription nor expression of the LT-ag was impaired by CDV. However, the drug reduced this website intracellular BKPyV DNA replication by >90% while at equivalent concentrations a reduction of cellular DNA replication and metabolic activity of 7% and 11%, respectively, in uninfected human renal tubular cells was found. Furthermore, BKPyV infection increased cellular DNA replication to 142% and metabolic activity to 116%, respectively, which were reduced by CDV to levels of uninfected untreated cells. Our laboratory Selleck EX 527 selected SV40 mutants resistant to CDV, following growth of the virus in increasing drug-concentration in the Monkey African green kidney epithelial cell line BSC-1. This system was used because the entire lytic replicative cycle of SV40 is accomplished. CDV-resistant viruses bear

mutations in the ORI and helicase domains of the LT-ag, indicating that the helicase activity required for viral DNA unwinding during replication may be affected by CDV (our unpublished data). Further research is required to prove that the helicase/ATPase activity of the LT-ag is affected by Adenosine CDV and/or its metabolites. Interference with the helicase/ATPase activity of the LT-ag may explain the activity of CDV during PyV productive infection but not against PyV-induced tumors. Liekens and collaborators reported the activity of CDV against cerebral hemangiomas induced following intraperitoneal inoculation of newborn rats with mouse PyV (Liekens et al., 1998). The drug was able to completely suppress hemangioma development even when applied 3 days following viral inoculation and resulted in 40% survival and delay in tumor-associated

mortality when treatment started at the time cerebral hemangiomas were macroscopically visible (i.e. 9 days post-viral infection). Infectious virus or viral DNA were not detected in the brain of the infected animals at any time post-infection, indicating that there was not viral replication in mouse PyV-infected rats and that an antitumor effect of CDV should be responsible for the activity of the drug in this model. A similar mode of action was postulated to explain the efficacy of CDV on the growth of hemangiosarcomas in mice originating from PyV-transformed (PV/2b/35) cells which do not produce infectious virus but express the viral T antigen (Liekens et al., 2001). CDV was also found to induce apoptosis in the hemangiosarcomas.