title: Unraveling the Mysterious Interactions Between Hepatitis C Virus RNA and Liver-Specific MicroRNA-122.
abstract: Many viruses encode or subvert cellular microRNAs (miRNAs) to aid in their gene expression, amplification strategies, or pathogenic signatures. miRNAs typically downregulate gene expression by binding to the 3' untranslated region of their mRNA targets. As a result, target mRNAs are translationally repressed and subsequently deadenylated and degraded. Curiously, hepatitis C virus (HCV), a member of the Flaviviridae family, recruits two molecules of liver-specific microRNA-122 (miR-122) to the 5' end of its genome. In contrast to the canonical activity of miRNAs, the interactions of miR-122 with the viral genome promote viral RNA accumulation in cultured cells and in animal models of HCV infection. Sequestration of miR-122 results in loss of viral RNA both in cell culture and in the livers of chronic HCV-infected patients. This review discusses the mechanisms by which miR-122 is thought to enhance viral RNA abundance and the consequences of miR-122-HCV interactions. We also describe preliminary findings from phase II clinical trials in patients treated with miR-122 antisense oligonucleotides.
authors: Department of Microbiology and Immunology, Stanford University, Stanford, California 94305.
authors: Peter
authors: P
authors: Sarnow
authors: Department of Microbiology and Immunology, McGill University, Montreal, Quebec H3A 2B4, Canada; email: selena.sagan@mcgill.ca.
authors: Selena M
authors: SM
authors: Sagan
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D060565:Argonaute Proteins / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D016679:Genome, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics*; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D034622:RNA Interference / Q000502:physiology*; D012367:RNA, Viral / Q000235:genetics*; D014779:Virus Replication / Q000235:genetics
chemical_list: D020413:3' Untranslated Regions; D060565:Argonaute Proteins; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral
keywords: Argonaute; HCV; RNA silencing; hepatitis C virus; miR-122; microRNA