PTBP1 and translation of diabetogenic viruses in beta cells

Glucose entry in the pancreatic beta cell triggers insulin secretion and the rapid biosynthesis of insulin granules (ISGs). We have shown that glucose and cAMP independently promote the nucleocytoplasmic translocation of polypyrimidine tract-binding protein (PTBP1) in beta cells (Knoch et al., 2004 and 2006). Cytosolic PTBP1 binds the mRNAs encoding ISG proteins, thus enhancing their stability and translation. PTBP1 can also foster the IRES-mediated translation of picornaviruses, including enteroviruses. Several prospective studies have suggested that enterovirus infection may trigger type 1 diabetes, Thus, we investigated whether diabetogenic enteroviruses hijack the machinery for ISG biogenesis, and in particular PTBP1, for their effective propagation in beta cells.

We show that PTBP1 binds to the 5'-UTR of the diabetogenic Echovirus-9 (EV-9) DM. The 5'-UTR of Echovirus-9 DM is more efficient in promoting translation than the 5'-UTR of the non-diabetogenic Echovirus-9 Barty. Using dual luciferase reporter assays we found that glucose stimulation of insulinoma cells increases the translation of EV-9 DM in a PTBP1-dependent fashion. Taken together, our findings support the hypothesis that diabetogenic enteroviruses exploit PTBP1 for their translation in beta cells, and thus may affect the turnover of ISGs.