title: Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing.
abstract: Homology-dependent RNA silencing occurs in many eukaryotic cells. We reported recently that nodaviral infection triggers an RNA silencing-based antiviral response (RSAR) in Drosophila, which is capable of a rapid virus clearance in the absence of expression of a virus-encoded suppressor. Here, we present further evidence to show that the Drosophila RSAR is mediated by the RNA interference (RNAi) pathway, as the viral suppressor of RSAR inhibits experimental RNAi initiated by exogenous double-stranded RNA and RSAR requires the RNAi machinery. We demonstrate that RNAi also functions as a natural antiviral immunity in mosquito cells. We further show that vaccinia virus and human influenza A, B, and C viruses each encode an essential protein that suppresses RSAR in Drosophila. The vaccinia and influenza viral suppressors, E3L and NS1, are distinct double-stranded RNA-binding proteins and essential for pathogenesis by inhibiting the mammalian IFN-regulated innate antiviral response. We found that the double-stranded RNA-binding domain of NS1, implicated in innate immunity suppression, is both essential and sufficient for RSAR suppression. These findings provide evidence that mammalian virus proteins can inhibit RNA silencing, implicating this mechanism as a nucleic acid-based antiviral immunity in mammalian cells.
authors.affiliation: Departments of Plant Pathology and Entomology and Microbiology Program, University of California, Riverside, CA 92521, USA.
authors.forename: Wan-Xiang
authors.initials: WX
authors.lastname: Li
authors.forename: Hongwei
authors.initials: H
authors.lastname: Li
authors.forename: Rui
authors.initials: R
authors.lastname: Lu
authors.forename: Feng
authors.initials: F
authors.lastname: Li
authors.forename: Monica
authors.initials: M
authors.lastname: Dus
authors.forename: Peter
authors.initials: P
authors.lastname: Atkinson
authors.forename: Edward W A
authors.initials: EW
authors.lastname: Brydon
authors.forename: Kyle L
authors.initials: KL
authors.lastname: Johnson
authors.forename: Adolfo
authors.initials: A
authors.lastname: García-Sastre
authors.forename: L Andrew
authors.initials: LA
authors.lastname: Ball
authors.forename: Peter
authors.initials: P
authors.lastname: Palese
authors.forename: Shou-Wei
authors.initials: SW
authors.lastname: Ding
mesh_terms: D000818:Animals; D001665:Binding Sites; D009033:Culicidae / Q000276:immunology; D004330:Drosophila / Q000276:immunology; D007113:Immunity, Innate; D007372:Interferons / Q000037:antagonists & inhibitors*; D009975:Orthomyxoviridae / Q000502:physiology*; D034622:RNA Interference; D014616:Vaccinia virus / Q000502:physiology*; D014764:Viral Proteins / Q000502:physiology*
chemical_list: D014764:Viral Proteins; D007372:Interferons