MiR-122: An Antiviral Target against Hepatitis C Virus

Abstract

microRNA-122 (miR-122), a liver specific microRNA, has been shown to facilitate the Hepatitis C virus (HCV) replication and/or translation. Although the exact role played by miR-122 in this process is not fully understood, it has been shown that one of the functions of miR-122 is to stabilize the HCV RNA genome upon binding. There are two miR-122 binding sites within the HCV genome 5'-untranslated region (5'-UTR), named the S1 and S2 sites, both containing the miR-122 seed sequence. It has been shown that miR-122 is a valid antiviral target, as locked nucleic acids developed against miR-122 abolished the HCV replication. However, miR-122 has numerous other functions in the hepatic cell, which will also be affected by these LNAs. In this study, we adopted a different approach, namely to design peptide nucleic acids (PNAs) against the miR-122 binding sites within the HCV genome, sites conserved in all HCV genotypes and to test their antiviral properties. Our results indicate that one such PNA designed against the site S2 binds to the 5'-UTR of the HCV genome. And moreover, has the ability to invade the miR-122/HCV 5'UTR complex, releasing miR-122.