Antiviral Response Interferon’s New Weapon

John F. Foley

Science’s STKE, AAAS, Washington, DC 20005, USA

MicroRNAs (miRNAs) are small noncoding RNAs that inhibit the expression of target genes by promoting mRNA degradation or inhibiting mRNA translation. In plants and invertebrates, miRNAs are involved in the innate immune response to viruses, but it was not known whether they performed a similar function in mammals. Type I interferons such as interferon- (IFN-) are antiviral cytokines that are crucial to host defense against virus infection, and Pedersen et al. investigated whether miRNAs might play a role in this response. The authors used microarrays to identify about 30 miRNAs with altered abundance in an IFN--treated compared with untreated human hepatoma-derived cell line (Huh7). The sequences of eight of these miRNAs showed complementarities with the hepatitis C virus (HCV) RNA genome. The abundance of miR-122, a liver-specific miRNA that is essential for HCV replication, was decreased in IFN--treated Huh7 cells compared with untreated cells. The authors transfected a modified Huh7 cell line that contained an autonomously replicating HCV genome with synthetic miRNA mimics of the IFN--induced HCV-specific miRNAs and found that HCV replication (as assessed by quantitative measurement of HCV RNA) was reduced by five of these miRNAs compared with that in control miRNA-transfected cells. Transfection of HCV-containing Huh7 cells with a mixture of inhibitors of these same five miRNAs attenuated the ability of IFN- to inhibit HCV replication. The addition of synthetic miR-122 further interfered with IFN--mediated inhibition of HCV replication. Together, these data show that miRNAs contribute to the antiviral effects of IFN-, highlighting a new component to host defense mechanisms against viruses.

I. M. Pedersen, G. Cheng, S. Wieland, S. Volinia, C. M. Croce, F. V. Chisari, M. David, Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449, 919-922 (2007). [PubMed]

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