title: The Ebola virus VP35 protein is a suppressor of RNA silencing.
abstract: RNA silencing or interference (RNAi) is a gene regulation mechanism in eukaryotes that controls cell differentiation and developmental processes via expression of microRNAs. RNAi also serves as an innate antiviral defence response in plants, nematodes, and insects. This antiviral response is triggered by virus-specific double-stranded RNA molecules (dsRNAs) that are produced during infection. To overcome antiviral RNAi responses, many plant and insect viruses encode RNA silencing suppressors (RSSs) that enable them to replicate at higher titers. Recently, several human viruses were shown to encode RSSs, suggesting that RNAi also serves as an innate defence response in mammals. Here, we demonstrate that the Ebola virus VP35 protein is a suppressor of RNAi in mammalian cells and that its RSS activity is functionally equivalent to that of the HIV-1 Tat protein. We show that VP35 can replace HIV-1 Tat and thereby support the replication of a Tat-minus HIV-1 variant. The VP35 dsRNA-binding domain is required for this RSS activity. Vaccinia virus E3L protein and influenza A virus NS1 protein are also capable of replacing the HIV-1 Tat RSS function. These findings support the hypothesis that RNAi is part of the innate antiviral response in mammalian cells. Moreover, the results indicate that RSSs play a critical role in mammalian virus replication.
authors.affiliation: Laboratory of Experimental Virology, Department of Medical Microbiology, Center of Infection and Immunity Amsterdam, Academic Medical Center of the University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Haasnoot
authors.forename: Walter
authors.initials: W
authors.lastname: de Vries
authors.forename: Ernst-Jan
authors.initials: EJ
authors.lastname: Geutjes
authors.forename: Marcel
authors.initials: M
authors.lastname: Prins
authors.forename: Peter
authors.initials: P
authors.lastname: de Haan
authors.forename: Ben
authors.initials: B
authors.lastname: Berkhout
mesh_terms: D000818:Animals; D001483:Base Sequence; D002522:Chlorocebus aethiops; D015696:Gene Products, tat / Q000502:physiology; D015497:HIV-1 / Q000502:physiology; D006801:Humans; D007113:Immunity, Innate; D007372:Interferons / Q000037:antagonists & inhibitors; D008969:Molecular Sequence Data; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins / Q000502:physiology*; D034622:RNA Interference; D012330:RNA, Double-Stranded / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000502:physiology; D015533:Transcriptional Activation; D014709:Vero Cells; D014758:Viral Core Proteins / Q000502:physiology*; D017361:Viral Nonstructural Proteins / Q000502:physiology; D014764:Viral Proteins / Q000502:physiology; D014777:Virus Diseases / Q000276:immunology*; D014779:Virus Replication; D054322:tat Gene Products, Human Immunodeficiency Virus
chemical_list: C081374:E3L protein, Vaccinia virus; D015696:Gene Products, tat; C085820:INS1 protein, influenza virus; D019590:Nucleocapsid Proteins; D009698:Nucleoproteins; D012330:RNA, Double-Stranded; D016601:RNA-Binding Proteins; D014758:Viral Core Proteins; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; C084818:nucleoprotein VP35, Ebola virus; D054322:tat Gene Products, Human Immunodeficiency Virus; D007372:Interferons