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Antiviral RNA Interference in Mammalian Cells
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Journal Article
Antiviral RNA Interference in Mammalian Cells
2013
Overview
In antiviral RNA interference (RNAi), the DICER enzyme processes virus-derived double-stranded RNA (dsRNA) into small interfering RNAs (siRNAs) that guide ARGONAUTE proteins to silence complementary viral RNA. As a counterdefense, viruses deploy viral suppressors of RNAi (VSRs). Well-established in plants and invertebrates, the existence of antiviral RNAi remains unknown in mammals. Here, we show that undifferentiated mouse cells infected with encephalomyocarditis virus (EMCV) or Nodamura virus (NoV) accumulate ~22-nucleotide RNAs with all the signature features of siRNAs. These derive from viral dsRNA replication intermediates, incorporate into AGO2, are eliminated in Dicer knockout cells, and decrease in abundance upon cell differentiation. Furthermore, genetically ablating a NoV-encoded VSR that antagonizes DICER during authentic infections reduces NoV accumulation, which is rescued in RNAi-deficient mouse cells. We conclude that antiviral RNAi operates in mammalian cells.
Publisher
American Association for the Advancement of Science,The American Association for the Advancement of Science
Subject
/ Argonaute Proteins - genetics
/ Argonaute Proteins - metabolism
/ Cardiovirus Infections - immunology
/ DEAD-box RNA Helicases - genetics
/ DEAD-box RNA Helicases - metabolism
/ Encephalomyocarditis virus - genetics
/ Encephalomyocarditis virus - physiology
/ Mammals
/ Mice
/ proteins
/ Ribonuclease III - metabolism
/ RNA
/ RNA Interference - immunology
/ RNA Virus Infections - immunology
/ RNA, Double-Stranded - genetics
/ RNA, Double-Stranded - immunology
/ RNA, Double-Stranded - metabolism
/ RNA, Small Interfering - genetics
/ RNA, Small Interfering - immunology
/ RNA, Small Interfering - metabolism
/ Viruses
