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

Nayak, Arabinda; Berry, Bassam; Tassetto, Michel; Kunitomi, Mark; Acevedo, Ashley; Deng, Changhui; Krutchinsky, Andrew N.; Gross, John D.; Antoniewski, Christophe; Andino, Raul

doi:10.1038/nsmb.1810

Cited by 196 publications

(275 citation statements)

References 47 publications

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“…Such discriminative action against long dsRNA and siRNA duplexes by a single protein is a unique property among the plant virus-encoded VSRs studied thus far and is also not evident in the B2 protein of invertebrate viruses such as Flock House virus (FHV) and Wuhan nodavirus (WhNV), which share several functional similarities with TCV P38, as uncovered here (Chao et al 2005;Qi et al 2011). Similarly, yet not discriminated, the dicistrovirus VSR, Drosophila C virus (DCV) 1A was shown to inhibit both Dcr2-mediated dsRNA processing and Ago2-RISC assembly (van Rij et al 2006;Nayak et al 2010). On the other hand, the closely related Cricket paralysis virus (CrPV) 1A does not share such dual functions of DCV-1A but acts as VSR by inhibiting Ago2-RISC-mediated slicing (Nayak et al 2010).…”

Section: Discussionmentioning

confidence: 94%

“…Similarly, yet not discriminated, the dicistrovirus VSR, Drosophila C virus (DCV) 1A was shown to inhibit both Dcr2-mediated dsRNA processing and Ago2-RISC assembly (van Rij et al 2006;Nayak et al 2010). On the other hand, the closely related Cricket paralysis virus (CrPV) 1A does not share such dual functions of DCV-1A but acts as VSR by inhibiting Ago2-RISC-mediated slicing (Nayak et al 2010).…”

Section: Discussionmentioning

confidence: 99%

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Biochemical and genetic functional dissection of the P38 viral suppressor of RNA silencing

Iki

Tschopp

Voinnet

2017

RNA

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Phytoviruses encode viral suppressors of RNA silencing (VSRs) to counteract the plant antiviral silencing response, which relies on virus-derived small interfering (si)RNAs processed by Dicer RNaseIII enzymes and subsequently loaded into ARGONAUTE (AGO) effector proteins. Here, a tobacco cell-free system was engineered to recapitulate the key steps of antiviral RNA silencing and, in particular, the most upstream double-stranded (ds)RNA processing reaction, not kinetically investigated thus far in the context of plant VSR studies. Comparative biochemical analyses of distinct VSRs in the reconstituted assay showed that in all cases tested, VSR interactions with siRNA duplexes inhibited the loading, but not the activity, of antiviral AGO1 and AGO2. Turnip crinkle virus P38 displayed the additional and unique property to bind both synthetic and RNA-dependent-RNA-polymerase-generated long dsRNAs, and inhibited the processing into siRNAs. Single amino acid substitutions in P38 could dissociate dsRNAprocessing from AGO-loading inhibition in vitro and in vivo, illustrating dual-inhibitory strategies discriminatively deployed within a single viral protein, which, we further show, are bona fide suppressor functions that evolved independently of the conserved coat protein function of P38.

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Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

Biochemical and genetic functional dissection of the P38 viral suppressor of RNA silencing

Iki

Tschopp

Voinnet

2017

RNA

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“…In addition, the pulled-down RNAs were sensitive to digestion with the dsRNA-specific enzyme RNaseIII, but not to the single-stranded (ss) RNA specific RNasesA and T1 ( Fig S2D). Double-stranded RNA was also readily detectable in cells infected with Cricket paralysis virus, a positive-strand RNA virus that encodes a suppressor of RNAi that does not interact with dsRNA (15) (Fig. S2E).…”

Section: Vsv Does Not Produce Detectable Amounts Of Dsrna In Mammalianmentioning

confidence: 95%

RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila

Mueller

Gausson

Vodovar

et al. 2010

Proc. Natl. Acad. Sci. U.S.A.

131

133

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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.deep sequencing | arbovirus | Dicer-2 | AGO2 | small RNA profiling

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“…Insect-infecting Flock House Virus (FHV) B2, Drosophila C virus DCV-1A, and cricket paralysis virus CrPV-1A proteins showed RNA silencing suppression activity in insect cells (Li et al 2002;Chao et al 2005;van Rij et al 2006;Nayak et al 2010), whereas human influenza A virus NS1 protein, human immunodeficiency virus type 1 Tat protein, and Ebola VP35 displayed RNA silencing suppression activity in cultured human cells (Bennasser et al 2005;Haasnoot et al 2007;Leung et al 2010). Cross-kingdom suppression of RNA silencing was observed for the FHV B2 protein and human influenza NS1 in plants (Li et al 2002;Bucher et al 2004;Cheng et al 2009;de Vries et al 2009).…”

Section: Introductionmentioning

confidence: 97%

Structural implications into dsRNA binding and RNA silencing suppression by NS3 protein of Rice Hoja Blanca Tenuivirus

Xia

Tan²,

Teh³

et al. 2011

RNA

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Rice Hoja Blanca Tenuivirus (RHBV), a negative strand RNA virus, has been identified to infect rice and is widely transmitted by the insect vector. NS3 protein encoded by RHBV RNA3 was reported to be a potent RNAi suppressor to counterdefense RNA silencing in plants, insect cells, and mammalian cells. Here, we report the crystal structure of the N-terminal domain of RHBV NS3 (residues 21-114) at 2.0 Å . RHBV NS3 N-terminal domain forms a dimer by two pairs of a-helices in an anti-parallel mode, with one surface harboring a shallow groove at the dimension of 20 Å 3 30 Å for putative dsRNA binding. In vitro RNA binding assay and RNA silencing suppression assay have demonstrated that the structural conserved residues located along this shallow groove, such as Arg50, His51, Lys77, and His85, participate in dsRNA binding and RNA silencing suppression. Our results provide the initial structural implications in understanding the RNAi suppression mechanism by RHBV NS3.

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

Cited by 196 publications

References 47 publications

Biochemical and genetic functional dissection of the P38 viral suppressor of RNA silencing

Biochemical and genetic functional dissection of the P38 viral suppressor of RNA silencing

RNAi-mediated immunity provides strong protection against the negative-strand RNA vesicular stomatitis virus in Drosophila

Structural implications into dsRNA binding and RNA silencing suppression by NS3 protein of Rice Hoja Blanca Tenuivirus

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