Interferon modulation of cellular microRNAs as an antiviral mechanism

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(1). Here we show that interferon beta (IFN beta) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFN beta-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFN beta-induced miRNAs reproduces the antiviral effects of IFN beta on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFN beta against HCV. In addition, we demonstrate that IFN beta 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(2). Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.