title: Interferon modulation of cellular microRNAs as an antiviral mechanism.
abstract: RNA interference through non-coding microRNAs (miRNAs) represents a vital component of the innate antiviral immune response in plants and invertebrate animals; however, a role for cellular miRNAs in the defence against viral infection in mammalian organisms has thus far remained elusive. Here we show that interferon beta (IFNbeta) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFNbeta-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFNbeta-induced miRNAs reproduces the antiviral effects of IFNbeta on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFNbeta against HCV. In addition, we demonstrate that IFNbeta treatment leads to a significant reduction in the expression of the liver-specific miR-122, an miRNA that has been previously shown to be essential for HCV replication. Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.
authors.affiliation: Department of Molecular Biology, University of California San Diego, La Jolla, California 92093, USA.
authors.forename: Irene M
authors.initials: IM
authors.lastname: Pedersen
authors.forename: Guofeng
authors.initials: G
authors.lastname: Cheng
authors.forename: Stefan
authors.initials: S
authors.lastname: Wieland
authors.forename: Stefano
authors.initials: S
authors.lastname: Volinia
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Croce
authors.forename: Francis V
authors.initials: FV
authors.lastname: Chisari
authors.forename: Michael
authors.initials: M
authors.lastname: David
mesh_terms: D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016679:Genome, Viral / Q000235:genetics; D016174:Hepacivirus / Q000235:genetics* / Q000276:immunology* / Q000502:physiology; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D007113:Immunity, Innate; D016899:Interferon-beta / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism*; D034622:RNA Interference; D012367:RNA, Viral / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral; D016899:Interferon-beta