RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila.
Activation of innate antiviral responses in multicellular organisms relies on the recognition of structural differences between viral and cellular RNAs. Double-stranded (ds)RNA, produced during viral replication, is a well-known activator of antiviral defenses and triggers interferon production in vertebrates and RNAi in invertebrates and plants. Previous work in mammalian cells indicates that negative-strand RNA viruses do not appear to generate dsRNA, and that activation of innate immunity is triggered by the recognition of the uncapped 5' ends of viral RNA. This finding raises the question whether antiviral RNAi, which is triggered by the presence of dsRNA in insects, represents an effective host-defense mechanism against negative-strand RNA viruses. Here, we show that the negative-strand RNA virus vesicular stomatitis virus (VSV) does not produce easily detectable amounts of dsRNA in Drosophila cells. Nevertheless, RNAi represents a potent response to VSV infection, as illustrated by the high susceptibility of RNAi-defective mutant flies to this virus. VSV-derived small RNAs produced in infected cells or flies uniformly cover the viral genome, and equally map the genome and antigenome RNAs, indicating that they derive from dsRNA. Our findings reveal that RNAi is not restricted to the defense against positive-strand or dsRNA viruses but can also be highly efficient against a negative-strand RNA virus. This result is of particular interest in view of the frequent transmission of medically relevant negative-strand RNA viruses to humans by insect vectors.
Mueller
Stefanie
S
Centre National de la Recherche Scientifique Unité Propre de Recherche 9022, Unité Propre de Recherche 9002, Institut de Biologie Moléculaire et Cellulaire du Centre National de la Recherche Scientifique UPR9002, 67084 Strasbourg, France.
Gausson
Valérie
V
Vodovar
Nicolas
N
Deddouche
Safia
S
Troxler
Laurent
L
Perot
Jonathan
J
Pfeffer
Sébastien
S
Hoffmann
Jules A
JA
Saleh
Maria-Carla
MC
Imler
Jean-Luc
JL
D000818:Animals; D002460:Cell Line; D004330:Drosophila / Q000821:virology; D016679:Genome, Viral; D007113:Immunity, Innate / Q000235:genetics*; D007303:Insect Vectors; D034622:RNA Interference / Q000276:immunology*; D012328:RNA Viruses / Q000276:immunology; D012330:RNA, Double-Stranded / Q000032:analysis; D012367:RNA, Viral; D018116:Vesiculovirus / Q000276:immunology*
D012330:RNA, Double-Stranded; D012367:RNA, Viral