1. Department of Molecular Biology,
2. Division of Biological Sciences, and,
3. Moores Cancer Center, University of California San Diego, La Jolla, California 92093, USA
4. Division of Experimental Pathology, The Scripps Research Institute, La Jolla, California 92037, USA
5. Department of Molecular Virology, Immunology & Medical Genetics, Ohio State University, Columbus, Ohio 43210, USA

Correspondence to: Michael David^1,2 Correspondence and requests for materials should be addressed to M.D. (Email: midavid@ucsd.edu).

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 elusive¹. Here we show that interferon beta (IFN) rapidly modulates the expression of numerous cellular miRNAs, and that eight of these IFN-induced miRNAs have sequence-predicted targets within the hepatitis C virus (HCV) genomic RNA. The introduction of synthetic miRNA-mimics corresponding to these IFN-induced miRNAs reproduces the antiviral effects of IFN on HCV replication and infection, whereas neutralization of these antiviral miRNAs with anti-miRNAs reduces the antiviral effects of IFN against HCV. In addition, we demonstrate that IFN 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.

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