Modulation of viral Internal Ribosome Entry Segments (IRES)

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The hepatitis C virus (HCV) infection continues to be of major clinical importance. HCV utilises a cap-independent process for initiation of translation, in which the ribosome is recruited to the mRNA by a highly structured ?internal ribosome entry segment? (IRES) in the 5?-untranslated region. Efficient translation apparently requires the presence of a bound trans-acting factor, polypyrimidine tract-binding protein (PTB). We will apply discrete chemical tools and chemical genetic techniques, including chemical induced dimerization, in order to gain in-depth molecular insights into the IRES-mediated translation and in particular the role of PTB.