title: Modulation of GB virus B RNA abundance by microRNA-122: dependence on and escape from microRNA-122 restriction.
abstract: Hepatitis C virus (HCV) RNA forms an unusual interaction with human microRNA-122 (miR-122) that promotes viral RNA accumulation in cultured human liver cells and in the livers of infected chimpanzees. GB virus B (GBV-B) is a hepatotropic virus and close relative of HCV. Thus, GBV-B has been used as a surrogate system to study HCV amplification in cultured cells and in infected tamarins. It was discovered that the 5'-terminal sequences of GBV-B RNA, like HCV RNA, forms an Argonaute 2-mediated complex with two miR-122 molecules that are essential for accumulation of GBV-B subgenomic replicon RNA. However, sequences in miR-122 that anneal to each viral RNA genome were different, suggesting distinct overall structural features in HCV:miR-122 and GBV-B:miR-122 complexes. Surprisingly, a deletion that removed both miR-122 binding sites from the subgenomic GBV-B RNAs rendered viral RNA amplification independent from miR-122 and Argonaute 2. This finding suggests that structural features at the end of the viral genome dictate whether miR-122 is required to aid in maintaining viral RNA abundance.
authors.affiliation: Department of Microbiology and Immunology, Stanford University School of Medicine, Stanford, California, USA. smsagan@stanford.edu
authors.forename: Selena M
authors.initials: SM
authors.lastname: Sagan
authors.forename: Peter
authors.initials: P
authors.lastname: Sarnow
authors.forename: Joyce A
authors.initials: JA
authors.lastname: Wilson
mesh_terms: D060565:Argonaute Proteins / Q000378:metabolism*; D015152:Blotting, Northern; D045744:Cell Line, Tumor; D017931:DNA Primers / Q000235:genetics; D029406:GB virus B / Q000235:genetics* / Q000378:metabolism; D015967:Gene Expression Regulation, Viral / Q000502:physiology*; D016174:Hepacivirus / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008156:Luciferases; D035683:MicroRNAs / Q000378:metabolism*; D016296:Mutagenesis; D010957:Plasmids / Q000235:genetics; D012367:RNA, Viral / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D012093:Replicon / Q000235:genetics; D014162:Transfection
chemical_list: C466422:AGO2 protein, human; D060565:Argonaute Proteins; D017931:DNA Primers; C531907:MIRN122 microRNA, human; D035683:MicroRNAs; D012367:RNA, Viral; D008156:Luciferases