title: Antiviral RNA interference in mammalian cells.
abstract: 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.
authors.affiliation: Department of Biology, Swiss Federal Institute of Technology Zurich (ETH-Z), Zurich, Switzerland.
authors.forename: P V
authors.initials: PV
authors.lastname: Maillard
authors.forename: C
authors.initials: C
authors.lastname: Ciaudo
authors.forename: A
authors.initials: A
authors.lastname: Marchais
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.forename: F
authors.initials: F
authors.lastname: Jay
authors.forename: S W
authors.initials: SW
authors.lastname: Ding
authors.forename: Olivier
authors.initials: O
authors.lastname: Voinnet
mesh_terms: D000818:Animals; D060565:Argonaute Proteins / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D018188:Cardiovirus Infections / Q000276:immunology*; D002460:Cell Line; D053487:DEAD-box RNA Helicases / Q000235:genetics / Q000378:metabolism; D004686:Encephalomyocarditis virus / Q000235:genetics / Q000502:physiology*; D055786:Gene Knockout Techniques; D051379:Mice; D008969:Molecular Sequence Data; D030381:Nodaviridae / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference / Q000276:immunology*; D012327:RNA Virus Infections / Q000276:immunology*; D012330:RNA, Double-Stranded / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D012367:RNA, Viral / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D043244:Ribonuclease III / Q000235:genetics / Q000378:metabolism; D014779:Virus Replication
chemical_list: C526735:Ago2 protein, mouse; D060565:Argonaute Proteins; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D012367:RNA, Viral; C509781:Dicer1 protein, mouse; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases