Gene regulation of Hepatitis C virus and Picornaviruses
Hepatitis C Virus (HCV) propagates preferentially in the liver. After infection of a cell, HCV and other single-stranded RNA viruses like Poliovirus, Rhinoviruses or Hepatitis A Virus use their positive strand genomic RNA directly for translation in the cytosol. The cis-elements for replication of the HCV RNA genome that direct the initiation of negative and positive strand RNA synthesis largely reside in the 5´- and 3´-untranslated regions (UTRs) flanking the viral polyprotein open reading frame (ORF). For the preferential translation of their own viral proteins, these viruses bypass the normal route of cap-dependent translation in the eukaryotic cell by a special mechanism. The initiation of translation of viral proteins is directed by a cis-acting region of the viral RNA, the internal ribosome entry site (IRES).
Both HCV translation and replication are stimulated by the liver-specific microRNA-122 (miR-122) and by cellular RNA-binding proteins which are usually not involved in translation. The interaction of miR-122 with the viral genome is mediated by Argonaute (Ago) proteins and results in stabilization of the RNA genome and enhanced translation, a function of a microRNA that is different from the canonical function of microRNAs in repressing the translation of cellular mRNAs. We investigate the interactions of these microRNAs and proteins with the viral genome and their effects on translation and replication of these viruses. These studies aim at a better understanding of the arrangement of the cis-elements involved in translation and replication of these viruses in the infected cells and of trans-acting factors binding to the viral RNA.