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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.

SUBMITTER: Nayak A 

PROVIDER: S-EPMC3815677 | biostudies-literature | 2010 May

REPOSITORIES: biostudies-literature

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Cricket paralysis virus antagonizes Argonaute 2 to modulate antiviral defense in Drosophila.

Nayak Arabinda A   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  

Nature structural & molecular biology 20100418 5


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  ...[more]

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