title: Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila.
abstract: Insect viruses have evolved strategies to control the host RNAi antiviral defense mechanism. In nature, Drosophila melanogaster C virus (DCV) infection causes low mortality and persistent infection, whereas the closely related cricket paralysis virus (CrPV) causes a lethal infection. We show that these viruses use different strategies to modulate the host RNAi defense machinery. The DCV RNAi suppressor (DCV-1A) binds to long double-stranded RNA and prevents processing by Dicer2. In contrast, the CrPV suppressor (CrPV-1A) interacts with the endonuclease Argonaute 2 (Ago2) and inhibits its activity without affecting the microRNA (miRNA)-Ago1-mediated silencing. We examined the link between viral RNAi suppressors and the outcome of infection using recombinant Sindbis viruses encoding either CrPV-1A or DCV-1A. Flies infected with Sindbis virus expressing CrPV-1A showed a marked increase in virus production, spread and mortality. In contrast, Sindbis pathogenesis was only modestly increased by expression of DCV- 1A. We conclude that RNAi suppressors function as virulence factors in insects and can target the Drosophila RNAi pathway at different points.
authors.affiliation: Department of Microbiology and Immunology, University of California, San Francisco, California, USA.
authors.forename: Arabinda
authors.initials: A
authors.lastname: Nayak
authors.forename: Bassam
authors.initials: B
authors.lastname: Berry
authors.forename: Michel
authors.initials: M
authors.lastname: Tassetto
authors.forename: Mark
authors.initials: M
authors.lastname: Kunitomi
authors.forename: Ashley
authors.initials: A
authors.lastname: Acevedo
authors.forename: Changhui
authors.initials: C
authors.lastname: Deng
authors.forename: Andrew
authors.initials: A
authors.lastname: Krutchinsky
authors.forename: John
authors.initials: J
authors.lastname: Gross
authors.forename: Christophe
authors.initials: C
authors.lastname: Antoniewski
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D060565:Argonaute Proteins; D002460:Cell Line; D004330:Drosophila / Q000235:genetics / Q000378:metabolism / Q000821:virology*; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054884:Host-Pathogen Interactions; D007304:Insect Viruses / Q000472:pathogenicity*; D035683:MicroRNAs / Q000378:metabolism; D008969:Molecular Sequence Data; D034622:RNA Interference; D034743:RNA-Induced Silencing Complex / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016415:Sequence Alignment; D014764:Viral Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex; D014764:Viral Proteins
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