Interferon modulation of cellular microRNAs as an antiviral mechanism

Abstract

Plants and invertebrates can use RNA silencing as a protective mechanism in viral infection. Now cellular microRNAs (miRNAs) have been found to have an antiviral function in mammalian cells too. Interferon-β is involved in the regulation of a number of cellular miRNAs in human cells, and eight of these are active against sequences on the hepatitis C virus. In addition, modulation of cellular miRNA levels are found to contribute significantly towards the antiviral effects of interferon-β, suggesting that they are a functioning component of the mammalian innate immune response. Plants and invertebrates can use RNA silencing as a protective mechanism in viral infection. Cellular microRNAs can have anti-viral activity also in mammalian cells, in this case by contributing to the antiviral effects of interferon beta against hepatitis C virus. 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 elusive1. Here we show that interferon beta (IFNβ) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFNβ-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFNβ-induced miRNAs reproduces the antiviral effects of IFNβ on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFNβ against HCV. In addition, we demonstrate that IFNβ 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 replication2. Therefore, our findings strongly support the notion that mammalian organisms too, through the interferon system, use cellular miRNAs to combat viral infections.