Mutation Analysis of the Hepatitis C Virus Internal Ribosome Entry Site and Its Implication in Translation Initiation

The translation of the HCV viral proteins represents a key step in the life-cycle of this virus. In recent years, the available experimental evidence has conclusively determined that the translation initiation process of HCV is principally controlled by the viral 5' Untranslated Region (5'UTR). The principal characteristic of this region is represented by the fact that it can fold upon itself to form a complex RNA secondary I tertiary structure (known as IRES). This structure acts as an internal docking site for selected elements of the eukaryotic translational machinery, such as eIF3 and the 40S ribosomal subunit, allowing the assembly of a correcr initiation complex on an internal AUG codon. The different RNA secondary structures that bind these elements are known as domain It III, and IV. Integrity of these structures is essential for translation to occur and the aim of this project is to identify and characterize selected RNA-protein interactions that are essential for this process. The characterization of these interactions will hopefully provide not only a better knowledge of the translation processes driven by IRES elements but also novel targets for the development of specific HCV translation inhibitors.