Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila.
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.
Nayak
Arabinda
A
Department of Microbiology and Immunology, University of California, San Francisco, California, USA.
Berry
Bassam
B
Tassetto
Michel
M
Kunitomi
Mark
M
Acevedo
Ashley
A
Deng
Changhui
C
Krutchinsky
Andrew
A
Gross
John
J
Antoniewski
Christophe
C
Andino
Raul
R
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*
C433807:AGO2 protein, Drosophila; D060565:Argonaute Proteins; D029721:Drosophila Proteins; D035683:MicroRNAs; D034743:RNA-Induced Silencing Complex; D014764:Viral Proteins
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