T ' proteins influence JC virus biology

The JC virus early mRNA is alternatively spliced to yield five transcripts that encode large T antigen, small t antigen, T'(135), T'(136), and T'(165). The splicing process is regulated differentially in transformed versus lytically infected cells and temporally during the course of a productive infection. The authors have identified a potential exonic splicing enhancer near the 3' end of the early viral mRNA that, when mutated, results in altered splice site usage; The authors have only recently begun investigating the function of the three T' proteins using genetic and biochemical approaches. These studies indicate that the T' proteins enhance viral DNA replication and bind differentially to the pRB family of cellular tumor suppressor proteins in vitro. Using a G418 selection scheme, the authors have created cell lines that express either T antigen or each of the T' proteins individually. Preliminary analyses of these lines suggest that T antigen may induce apoptosis in rodent cells, an activity that may be blocked by other JC virus early proteins. Furthermore, examination of protein-protein interactions within the G418-selected cells reveal differences in binding of the viral proteins to the pRB family members relative to that seen in vitro.