RNA Silencing and its Suppressors in the Plant‐virus Interplay

Abstract

Viruses are obligate intracellular parasites that need to evade the host defences targeted against them. In plants, activation of ribonucleic acid (RNA) silencing is among the most powerful responses against viruses. To overcome this defence, both deoxyribonucleic acid (DNA) and RNA plant viruses make use of viral products able to interfere with silencing mechanisms, and known collectively as RNA silencing suppressors (RSSs). RSSs present an extraordinary diversity in modes of action, and therefore, their study is providing valuable information about the different silencing pathways in plants. This article reviews our knowledge on RSSs, including the experimental systems used to identify them, and the mechanisms by which they act. Finally, the additional effects that they cause in the network of silencing pathways, and hence the need of a tight control of their activity, are also considered.

Key concepts:

  • Argonaute: Family of proteins that contain certain conserved domains, such as PIWI domain (found in Piwi, or P‐element‐induced wimpy testis in Drosophila, and related proteins) and PAZ domain (found in Piwi, Argonaute and Zwille proteins). Proteins of this family are the main components of RNA silencing effector complexes.

  • Dicer: Ribonuclease belonging to the RNase III family. Dicer‐like enzymes cleave hairpin or double‐strand RNA molecules into short RNA duplexes of 20–24 nucleotides with a 2‐nucleotides overhang at the 3′ ends, which are key components of the RNA silencing pathways.

  • microRNA (miRNA): Endogenous single‐strand RNA of 20–21 nucleotides, which derives from a hairpin precursor. miRNAs are incorporated into RISC, guiding it, by base complementary, to silence endogenous mRNAs.

  • RNA‐dependent RNA polymerase (RdRP, RDR): Enzyme able to synthesize RNA using RNA as template. These enzymes are involved in amplification steps of RNA silencing.

  • RNA‐induced silencing complex (RISC): Multicomponent complex including an Argonaute protein and a short RNA. RISC can silence mRNAs by endonucleolytic cleavage, decay acceleration and translation inhibition.

  • RNA‐induced transcriptional silencing complex (RITS): Multicomponent complex including an Argonaute protein and a short RNA that silence gene expression by inhibiting or downregulating the transcription activity.

  • RNA silencing: General term used to describe different events triggered by small RNAs to induce transcriptional or posttranscriptional gene downregulation in a sequence‐homology manner.

  • RNA silencing suppressor (RSS): Factor (usually a protein) with the capacity to interfere with the onset of RNA silencing or with its maintenance. The expression of viral RSSs is the most common strategy that plant viruses use to escape from RNA silencing.

  • Short interfering RNA (siRNA): Small RNA of 20–24 nucleotides derived from Dicer‐mediated cleavage of a double‐stranded RNA precursor. One of the strands of the siRNA is incorporated in RISC or RITS to guide their RNA silencing effector activities.

Keywords: RNA silencing; silencing suppression; antiviral resistance; plant defence

Figure 1.

Schematic representation of key steps of plant virus‐related RNA silencing. The silencing components that are targeted by some RSSs (depicted as red ovals with their abbreviations inside) are also indicated. See text for details.

Figure 2.

Agro‐infiltration assay for assessing the RNA silencing suppression activity of the P1b protein of the ipomovirus CVYV (Valli et al., ). (a) Co‐infiltration with A. tumefaciens strains expressing GFP and CVYV P1b allows to maintain high levels of GFP at late time post‐infiltration in N. benthamiana leaves. (b) Infiltration of A. tumefaciens expressing GFP in GFP‐transformed N. benthamiana line 16c induces the silencing of both exogenous and endogenous GFP transgenes. RNA silencing spread from cell to cell is manifested by a narrow red ring around the infiltrated spot (Voinnet and Baulcombe, ) (vector, black arrows), and can be disturbed by RSSs, for instance CVYV P1b (P1b, white arrows). (c) RNA silencing also spreads to upper nonagroinfiltrated leaves, and some silencing suppressors are able to block this systemic spread. The picture shows that, in spite of the strong local silencing suppression activity of CVYV P1b, this RSS is not able to prevent systemic silencing (red veins reveal silencing of the endogenous GFP transgene in the upper leaves). GFP fluorescence pictures were taken under UV irradiation.

Figure 3.

Schematic representations of some RNA silencing suppression assays. (a) RNA silencing suppression in grafted transgenic plants. RNA silencing spreads from a transgene‐silenced rootstock to scions obtained from plants actively expressing a homologous transgene (I; the minus signs indicate RSS absence, or co‐expression of an RSS candidate lacking detectable RNA silencing suppression activities). Transgenic coexpression of some RSSs in the rootstock (RSSl+s+) prevents local silencing in the rootstock and spreading of a systemic silencing signal to the scion (II). Some other RSSs (RSSl+s) prevent local silencing but do not interfere with silencing spread (III). It is also possible that an RSS (RSSls+) that does not affect local silencing is able to block the systemic spread of the silencing signal (IV). (b) Complementation of a defective mutant virus. RNA silencing suppression activity of an RSS candidate can be inferred from its ability to complement the movement defect of a mutant virus lacking its own RSS. The use of a recombinant virus expressing a reporter gene, for instance GFP, makes easier the assay. (c) Enhancement of PVX pathogenicity. Whereas PVX infection provokes mild symptoms in Nicotiana plants, recombinant PVX viruses expressing RSSs usually cause much more severe symptoms. (d) Genetic approaches to identify and to analyse RSSs. Transgenic plants expressing an RSS (transgenic RSS+) could show ‘symptoms’ resembling those displayed by infected plants (Wt+Wt virus), and those of a mutant plant defective in the silencing factor targeted by the RSS (silencing factor). Infection of wild‐type plants with a mutant virus defective in the silencing suppressor (Wt+ΔRSS virus) does not produce typical symptoms and gives rise to low viral accumulation levels (represented by small number of red wavy lines). The RSS‐defective virus infects the plant defective in the RSS target (silencing factor+ΔRSS virus) with similar efficiency than the wild‐type virus infects the wild‐type plant.

Figure 4.

Schematic representation of diverse antisilencing mechanisms used by viral RSSs. (a) RSSs able to bind long RNA duplexes can protect these molecules against DCL processing. (b) Sequestering of double‐stranded small RNA by RSS complexes interferes with effector activities. (c) Begomoviral AC4 is the unique RSS described to date showing high affinity by single‐stranded small RNA. (d) Direct interaction between cucumoviral 2b and AGO1 prevents RISC effector action. (e) Poleroviral P0 is an F‐box protein able to form an SCF active complex that mediates AGO1 degradation.

Figure 5.

RSS expression can disturb plant development. Developmental defects induced in transgenic A. thaliana plants expressing the RSSs P1b from the ipomovirus CVYV and P1‐HCPro from the potyvirus PPV (Valli and García, unpublished results). Bars, 5 mm.

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References

Alamillo JM, Saenz P and Garcia JA (2006) Salicylic acid‐mediated and RNA‐silencing defense mechanisms cooperate in the restriction of systemic spread of Plum pox virus in tobacco. Plant Journal 48: 217–227.

Anandalakshmi R, Marathe R, Ge X et al. (2000) A calmodulin‐related protein that suppresses posttranscriptional gene silencing in plants. Science 290: 142–144.

Anandalakshmi R, Pruss GJ, Ge X et al. (1998) A viral suppressor of gene silencing in plants. Proceedings of the National Academy of Sciences of the USA 95: 13079–13084.

Andersson MG, Haasnoot PC, Xu N et al. (2005) Suppression of RNA interference by adenovirus virus‐associated RNA. Journal of Virology 79: 9556–9565.

Aparicio O, Razquin N, Zaratiegui M, Narvaiza I and Fortes P (2006) Adenovirus virus‐associated RNA is processed to functional interfering RNAs involved in virus production. Journal of Virology 80: 1376–1384.

Ballut L, Drucker M, Pugnière M et al. (2005) HcPro, a multifunctional protein encoded by a plant RNA virus, targets the 20S proteasome and affects its enzymic activities. Journal of General Virology 86: 2595–2603.

Baulcombe D (2005) RNA silencing. Trends in Biochemical Sciences 30: 290–293.

Baumberger N and Baulcombe DC (2005) Arabidopsis ARGONAUTE1 is an RNA slicer that selectively recruits microRNAs and short interfering RNAs. Proceedings of the National Academy of Sciences of the USA 102: 11928–11933.

Baumberger N, Tsai CH, Lie M, Havecker E and Baulcombe DC (2007) The polerovirus silencing suppressor P0 targets ARGONAUTE proteins for degradation. Current Biology 17: 1609–1614.

Bayne EH, Rakitina DV, Morozov SY and Baulcombe DC (2005) Cell‐to‐cell movement of Potato Potexvirus X is dependent on suppression of RNA silencing. Plant Journal 44: 471–482.

Bazzini AA, Hopp HE, Beachy RN and Asurmendi S (2007) Infection and coaccumulation of tobacco mosaic virus proteins alter microRNA levels, correlating with symptom and plant development. Proceedings of the National Academy of Sciences of the USA 104: 12157–12162.

Béclin C, Berthomé R, Palauqui J‐C, Tepfer M and Vaucheret H (1998) Infection of tobacco or Arabidopsis plants by CMV counteracts systemic post‐transcriptional silencing of nonviral (Trans)genes. Virology 252: 313–317.

Bennasser Y, Le SY, Benkirane M and Jeang KT (2005) Evidence that HIV‐1 encodes an siRNA and a suppressor of RNA silencing. Immunity 22: 607–619.

Blevins T, Rajeswaran R, Shivaprasad PV et al. (2006) Four plant dicers mediate viral small RNA biogenesis and DNA virus induced silencing. Nucleic Acids Research 34: 6233–6246.

Borsani O, Zhu JH, Verslues PE, Sunkar R and Zhu JK (2005) Endogenous siRNAs derived from a pair of natural cis‐antisense transcripts regulate salt tolerance in Arabidopsis. Cell 123: 1279–1291.

Bortolamiol D, Pazhouhandeh M, Marrocco K, Genschik P and Ziegler‐Graff V (2007) The polerovirus F box protein P0 targets ARGONAUTE1 to suppress RNA silencing. Current Biology 17: 1615–1621.

Bouché N, Lauressergues D, Gasciolli V and Vaucheret H (2006) An antagonistic function for Arabidopsis DCL2 in development and a new function for DCL4 in generating viral siRNAs. EMBO Journal 25: 3347–3356.

Brennecke J, Aravin AA, Stark A et al. (2007) Discrete small RNA‐generating loci as master regulators of transposon activity in Drosophila. Cell 128: 1089–1103.

Brigneti G, Voinnet O, Li WX et al. (1998) Viral pathogenicity determinants are suppressors of transgene silencing in Nicotiana benthamiana. EMBO Journal 17: 6739–6746.

Brodersen P, Sakvarelidze‐Achard L, Bruun‐Rasmussen M et al. (2008) Widespread translational inhibition by plant miRNAs and siRNAs. Science 320: 1185–1190.

Bucher E, Hemmes H, de Haan P, Goldbach R and Prins M (2004) The influenza A virus NS1 protein binds small interfering RNAs and suppresses RNA silencing in plants. Journal of General Virology 85: 983–991.

Bucher E, Sijen T, de Haan P, Goldbach R and Prins M (2003) Negative‐strand tospoviruses and tenuiviruses carry a gene for a suppressor of gene silencing at analogous genomic positions. Journal of Virology 77: 1329–1336.

Buck KW (1996) Comparison of the replication of positive‐stranded RNA viruses of plants and animals. In: Maramorosch K, Murphy FA and Shatkin AJ (eds) Advances in Virus Research, V, pp. 159–251. San Diego, CA: Academic Press Inc.

Cañizares MC, Navas‐Castillo J and Moriones E (2008) Multiple suppressors of RNA silencing encoded by both genomic RNAs of the crinivirus, Tomato chlorosis virus. Virology 379: 168–174.

Canto T, Uhrig JF, Swanson M, Wright KM and MacFarlane SA (2006) Translocation of Tomato bushy stunt virus P19 protein into the nucleus by ALY proteins compromises its silencing suppressor activity. Journal of Virology 80: 9064–9072.

Cao XS, Zhou P, Zhang XM et al. (2005) Identification of an RNA silencing suppressor from a plant double‐stranded RNA virus. Journal of Virology 79: 13018–13027.

Carbonell A, de Alba AEM, Flores R and Gago S (2008) Double‐stranded RNA interferes in a sequence‐specific manner with the infection of representative members of the two viroid families. Virology 371: 44–53.

Carrington JC, Kasschau KD and Johansen LK (2001) Activation of suppression of RNA silencing by plant viruses. Virology 281: 1–5.

Chao JA, Lee JH, Chapados BR et al. (2005) Dual modes of RNA‐silencing suppression by flock house virus protein B2. Nature Structural & Molecular Biology 12: 952–957.

Chapman EJ and Carrington JC (2007) Specialization and evolution of endogenous small RNA pathways. Nature Reviews. Genetics 8: 884–896.

Chapman EJ, Prokhnevsky AI, Gopinath K, Dolja VV and Carrington JC (2004) Viral RNA silencing suppressors inhibit the microRNA pathway at an intermediate step. Genes & Development 18: 1179–1186.

Chellappan P, Vanitharani R and Fauquet CM (2004) Short interfering RNA accumulation correlates with host recovery in DNA virus‐infected hosts, and gene silencing targets specific viral sequences. Journal of Virology 78: 7465–7477.

Chellappan P, Vanitharani R and Fauquet CM (2005) MicroRNA‐binding viral protein interferes with Arabidopsis development. Proceedings of the National Academy of Sciences of the USA 102: 10381–10386.

Chen HY, Yang J, Lin CQ and Adam Yuan Y (2008a) Structural basis for RNA‐silencing suppression by Tomato aspermy virus protein 2b. EMBO Reports 9: 754–760.

Chen J, Li WX, Xie DX, Peng JR and Ding SW (2004) Viral virulence protein suppresses RNA silencing‐mediated defense but upregulates the role of microRNA in host gene expression. Plant Cell 16: 1302–1313.

Chen WX, Zhang ZZ, Chen J et al. (2008b) HCV core protein interacts with dicer to antagonize RNA silencing. Virus Research 133: 250–258.

Cheng YQ, Liu ZM, Xu J et al. (2008) HC‐Pro protein of sugar cane mosaic virus interacts specifically with maize ferredoxin‐5 in vitro and in planta. Journal of General Virology 89: 2046–2054.

Chiba M, Reed JC, Prokhnevsky AI et al. (2006) Diverse suppressors of RNA silencing enhance agroinfection by a viral replicon. Virology 346: 7–14.

Chu M, Desvoyes B, Turina M, Noad R and Scholthof HB (2000) Genetic dissection of tomato bushy stunt virus p19‐protein‐mediated host‐dependent symptom induction and systemic invasion. Virology 266: 79–87.

Covey SN, Al‐Kaff N, Lángara A and Turner DS (1997) Plants combat infection by gene silencing. Nature 385: 781–782.

Csorba T, Bovi A, Dalmay T and Burgyán J (2007) The p122 subunit of Tobacco mosaic virus replicase is a potent silencing suppressor and compromises both small interfering RNA‐ and microRNA‐mediated pathways. Journal of Virology 81: 11768–11780.

Cui X, Li G, Wang D, Hu D and Zhou X (2005) A begomovirus DNAβ‐encoded protein binds DNA, functions as a suppressor of RNA silencing, and targets the cell nucleus. Journal of Virology 79: 10764–10775.

Curtin SJ, Watson JM, Smith NA et al. (2008) The roles of plant dsRNA‐binding proteins in RNAi‐like pathways. FEBS Letters 582: 2753–2760.

Dalmay T, Hamilton A, Mueller E and Baulcombe DC (2000) Potato virus X amplicons in Arabidopsis mediate genetic and epigenetic gene silencing. Plant Cell 12: 369–379.

Deleris A, Gallego‐Bartolome J, Bao JS et al. (2006) Hierarchical action and inhibition of plant dicer‐like proteins in antiviral defense. Science 313: 68–71.

Delgadillo MO, Sáenz P, Salvador B, García JA and Simón‐Mateo C (2004) Human influenza virus NS1 protein enhances viral pathogenicity and acts as an RNA silencing suppressor in plants. Journal of General Virology 85: 993–999.

Diaz‐Pendon JA, Li F, Li WX and Ding SW (2007) Suppression of antiviral silencing by cucumber mosaic virus 2b protein in Arabidopsis is associated with drastically reduced accumulation of three classes of viral small interfering RNAs. Plant Cell 19: 2053–2063.

Ding SW and Voinnet O (2007) Antiviral immunity directed by small RNAs. Cell 130: 413–426.

Ding XS, Liu JZ, Cheng NH et al. (2004) The Tobacco mosaic virus 126‐kDa protein associated with virus replication and movement suppresses RNA silencing. Molecular Plant–Microbe Interactions 17: 583–592.

Donaire L, Barajas D, Martinez‐Garcia B et al. (2008) Structural and genetic requirements for the biogenesis of Tobacco rattle virus‐derived small interfering RNAs. Journal of Virology 82: 5167–5177.

Dong Z, Han MH and Fedoroff N (2008) The RNA‐binding proteins HYL1 and SE promote accurate in vitro processing of pri‐miRNA by DCL1. Proceedings of the National Academy of Sciences of the USA 105: 9970–9975.

Dorokhov YL (2007) Gene silencing in plants. Molecular Biology 41: 519–530.

Dougherty WG and Parks TD (1995) Transgenes and gene suppression: telling us something new? Current Opinion in Cell Biology 7: 399–405.

Du QS, Duan CG, Zhang ZH et al. (2007) DCL4 targets Cucumber mosaic virus satellite RNA at novel secondary structures. Journal of Virology 81: 9142–9151.

Duan CG, Wang CH, Fang RX and Guo HS (2008) Artificial microRNAs highly accessible to targets confer efficient virus resistance in plants. Journal of Virology 82: 11084–11095.

Dunoyer P, Himber C, Ruiz‐Ferrer V, Alioua A and Voinnet O (2007) Intra‐ and intercellular RNA interference in Arabidopsis thaliana requires components of the microRNA and heterochromatic silencing pathways. Nature Genetics 39: 848–856.

Dunoyer P, Himber C and Voinnet O (2005) DICER‐LIKE 4 is required for RNA interference and produces the 21‐nucleotide small interfering RNA component of the plant cell‐to‐cell silencing signal. Nature Genetics 37: 1356–1360.

Dunoyer P, Himber C and Voinnet O (2006) Induction, suppression and requirement of RNA silencing pathways in virulent Agrobacterium tumefaciens infections. Nature Genetics 38: 258–263.

Dunoyer P, Lecellier CH, Parizotto EA, Himber C and Voinnet O (2004) Probing the microRNA and small interfering RNA pathways with virus‐encoded suppressors of RNA silencing. Plant Cell 16: 1235–1250.

Dunoyer P, Pfeffer S, Fritsch C et al. (2002) Identification, subcellular localization and some properties of a cysteine‐rich suppressor of gene silencing encoded by peanut clump virus. Plant Journal 29: 555–567.

Dunoyer P and Voinnet O (2008) Mixing and matching: the essence of plant systemic silencing? Trends in Genetics 24: 151–154.

Ebhardt HA, Thi EP, Wang MB and Unrau PJ (2005) Extensive 3′ modification of plant small RNAs is modulated by helper component‐proteinase expression. Proceedings of the National Academy of Sciences of the USA 102: 13398–13403.

El‐Shami M, Pontier D, Lahmy S et al. (2007) Reiterated WG/GW motifs form functionally and evolutionarily conserved ARGONAUTE‐binding platforms in RNAi‐related components. Genes & Development 21: 2539–2544.

English JJ, Mueller E and Baulcombe DC (1996) Suppression of virus accumulation in transgenic plants exhibiting silencing of nuclear genes. Plant Cell 8: 179–188.

Farazi TA, Juranek SA and Tuschl T (2008) The growing catalog of small RNAs and their association with distinct Argonaute/Piwi family members. Development 135: 1201–1214.

Fenner BJ, Goh W and Kwang J (2006) Sequestration and protection of double‐stranded RNA by the betanodavirus B2 protein. Journal of Virology 80: 6822–6833.

Förstemann K, Horwich MD, Wee L, Tomari Y and Zamore PD (2007) Drosophila microRNAs are sorted into functionally distinct argonaute complexes after production by Dicer‐1. Cell 130: 287–297.

Fusaro AF, Matthew L, Smith NA et al. (2006) RNA interference‐inducing hairpin RNAs in plants act through the viral defence pathway. EMBO Reports 7: 1168–1175.

García JA and Simón‐Mateo C (2006) A micropunch against plant viruses. Nature Biotechnology 24: 1358–1359.

Gasciolli V, Mallory AC, Bartel DP and Vaucheret H (2005) Partially redundant functions of Arabidopsis DICER‐like enzymes and a role for DCL4 in producing trans‐acting siRNAs. Current Biology 15: 1494–1500.

Gazzani S, Lawrenson T, Woodward C, Headon D and Sablowski R (2004) A link between mRNA turnover and RNA interference in Arabidopsis. Science 306: 1046–1048.

Ghazala W, Waltermann A, Pilot R, Winter S and Varrelmann M (2008) Functional characterization and subcellular localization of the 16 K cysteine‐rich suppressor of gene silencing protein of tobacco rattle virus. Journal of General Virology 89: 1748–1758.

Glazov E, Phillips K, Budziszewski GJ, Meins F and Levin JZ (2003) A gene encoding an RNase D exonuclease‐like protein is required for post‐transcriptional silencing in Arabidopsis. Plant Journal 35: 342–349.

Glick E, Zrachya A, Levy Y et al. (2008) Interaction with host SGS3 is required for suppression of RNA silencing by tomato yellow leaf curl virus V2 protein. Proceedings of the National Academy of Sciences USA 105: 157–161.

Gong Z, Morales‐Ruiz T, Ariza RR et al. (2002) ROS1, a repressor of transcriptional gene silencing in Arabidopsis, encodes a DNA glycosylase/lyase. Cell 111: 803–814.

Goto K, Kobori T, Kosaka Y, Natsuaki T and Masuta C (2007) Characterization of silencing suppressor 2b of Cucumber mosaic virus based on examination of its small RNA‐binding abilities. Plant and Cell Physiology 48: 1050–1060.

Gottwein E and Cullen BR (2008) Viral and cellular microRNAs as determinants of viral pathogenesis and immunity. Cell Host & Microbe 3: 375–387.

Gunawardane LS, Saito K, Nishida KM et al. (2007) A slicer‐mediated mechanism for repeat‐associated siRNA 5′ end formation in Drosophila. Science 315: 1587–1590.

Guo D, Spetz C, Saarma M and Valkonen JP (2003) Two potato proteins, including a novel RING finger protein (HIP1), interact with the potyviral multifunctional protein HCpro. Molecular Plant–Microbe Interactions 16: 405–410.

Guo HS and Ding SW (2002) A viral protein inhibits the long range signaling activity of the gene silencing signal. EMBO Journal 21: 398–407.

Gy I, Gasciolli V, Lauressergues D et al. (2007) Arabidopsis FIERY1, XRN2, and XRN3 are endogenous RNA silencing suppressors. Plant Cell 19: 3451–3461.

Haas G, Azevedo J, Moissiard G et al. (2008) Nuclear import of CaMV P6 is required for infection and suppression of the RNA silencing factor DRB4. EMBO Journal 27: 2102–2112.

Haasnoot J, de Vries W, Geutjes EJ et al. (2007) The Ebola virus VP35 protein is a suppressor of RNA silencing. PLoS Pathogens 3: e86.

Hagiwara‐Komoda Y, Hirai K, Mochizuki A et al. (2008) Overexpression of a host factor TOM1 inhibits Tomato mosaic virus propagation and suppression of RNA silencing. Virology 376: 132–139.

Hamilton AJ and Baulcombe DC (1999) A species of small antisense RNA in posttranscriptional gene silencing in plants. Science 286: 950–952.

Hammond TM, Andrewski MD, Roossinck MJ and Keller NP (2008) Aspergillus mycoviruses are targets and suppressors of RNA silencing. Eukaryotic Cell 7: 350–357.

Han MH, Goud S, Song L and Fedoroff N (2004) The Arabidopsis double‐stranded RNA‐binding protein HYL1 plays a role in microRNA‐mediated gene regulation. Proceedings of the National Academy of Sciences of the USA 101: 1093–1098.

Hao LH, Wang H, Sunter G and Bisaro DM (2003) Geminivirus AL2 and L2 proteins interact with and inactivate SNF1 kinase. Plant Cell 15: 1034–1048.

Havelda Z, Hornyik C, Crescenzi A and Burgyan J (2003) In situ characterization of Cymbidium ringspot tombusvirus infection‐induced posttranscriptional gene silencing in Nicotiana benthamiana. Journal of Virology 77: 6082–6086.

Havelda Z, Várallyay É, Válóczi A and Burgyán J (2008) Plant virus infection‐induced persistent host gene downregulation in systemically infected leaves. Plant Journal 55: 278–288.

Hemmes H, Lakatos L, Goldbach R, Burgyan J and Prins M (2007) The NS3 protein of Rice hoja blanca tenuivirus suppresses RNA silencing in plant and insect hosts by efficiently binding both siRNAs and miRNAs. RNA 13: 1079–1089.

Herr AJ, Molnar A, Jones A and Baulcombe DC (2006) Defective RNA processing enhances RNA silencing and influences flowering of Arabidopsis. Proceedings of the National Academy of Sciences of the USA 103: 10994–15001.

Hiraguri A, Itoh R, Kondo N et al. (2005) Specific interactions between dicer‐like proteins and HYL1/DRB‐family dsRNA‐binding proteins in Arabidopsis thaliana. Plant Molecular Biology 57: 173–188.

Ho T, Pallett D, Rusholme R, Dalmay T and Wang H (2006) A simplified method for cloning of short interfering RNAs from Brassica juncea infected with Turnip mosaic potyvirus and Turnip crinkle carmovirus. Journal of Virological Methods 136: 217–223.

Ho T, Wang H, Pallett D and Dalmay T (2007) Evidence for targeting common siRNA hotspots and GC preference by plant dicer‐like proteins. FEBS Letters 581: 3267–3272.

Höck J and Meister G (2008) The argonaute protein family. Genome Biology 9: 210–218.

Huang J, Wang F, Argyris E et al. (2007) Cellular microRNAs contribute to HIV‐1 latency in resting primary CD4+ T lymphocytes. Nature Medicine 13: 1241–1247.

Hutvágner G and Zamore PD (2002) A microRNA in a multiple‐turnover RNAi enzyme complex. Science 297: 2056–2060.

Itaya A, Zhong XH, Bundschuh R et al. (2007) A structured viroid RNA serves as a substrate for dicer‐like cleavage to produce biologically active small RNAs but is resistant to RNA‐induced silencing complex‐mediated degradation. Journal of Virology 81: 2980–2994.

Iwamoto T, Mise K, Takeda A et al. (2005) Characterization of striped jack nervous necrosis virus subgenomic RNA3 and biological activities of its encoded protein B2. Journal of General Virology 86: 2807–2816.

Ji J, Glaser A, Wernli M et al. (2008) Suppression of short interfering RNA‐mediated gene silencing by the structural proteins of hepatitis C virus. Journal of General Virology 89: 2761–2766.

Ji LH and Ding SW (2001) The suppressor of transgene RNA silencing encoded by Cucumber mosaic virus interferes with salicylic acid‐mediated virus resistance. Molecular Plant–Microbe Interactions 14: 715–724.

Jin HL (2008) Endogenous small RNAs and antibacterial immunity in plants. FEBS Letters 582: 2679–2684.

Jin YS, Ma DY, Dong JL et al. (2007a) HC‐Pro protein of Potato Virus Y can interact with three Arabidopsis 20S proteasome subunits in planta. Journal of Virology 81: 12881–12888.

Jin YS, Ma DY, Dong JL et al. (2007b) The HC‐Pro protein of Potato virus Y interacts with NtMinD of tobacco. Molecular Plant–Microbe Interactions 20: 1505–1511.

Johansen LK and Carrington JC (2001) Silencing on the spot. Induction and suppression of RNA silencing in the Agrobacterium‐mediated transient expression system. Plant Physiology 126: 930–938.

Jopling CL, Yi MK, Lancaster AM, Lemon SM and Sarnow P (2005) Modulation of hepatitis C virus RNA abundance by a liver‐specific microRNA. Science 309: 1577–1581.

Kachroo P, Yoshioka K, Shah J, Dooner HK and Klessig DF (2000) Resistance to Turnip crinkle virus in Arabidopsis is regulated by two host genes and is salicylic acid dependent but NPR1, ethylene, and jasmonate independent. Plant Cell 12: 677–690.

Kalantidis K, Schurnacher HT, Alexiadis T and Helm JM (2008) RNA silencing movement in plants. Biology of the Cell 100: 13–26.

Kapoor A, Agarwal M, Andreucci A et al. (2005) Mutations in a conserved replication protein suppress transcriptional gene silencing in a DNA‐methylation‐independent manner in Arabidopsis. Current Biology 15: 1912–1918.

Kasschau KD and Carrington JC (1998) A counterdefensive strategy of plant viruses: suppression of posttranscriptional gene silencing. Cell 95: 461–470.

Kasschau KD and Carrington JC (2001) Long‐distance movement and replication maintenance functions correlate with silencing suppression activity of potyviral HC‐Pro. Virology 285: 71–81.

Kasschau KD, Xie ZX, Allen E et al. (2003) P1/HC‐Pro, a viral suppressor of RNA silencing, interferes with Arabidopsis development and miRNA function. Developmental Cell 4: 205–217.

Katiyar‐Agarwal S, Gao S, Vivian‐Smith A and Jin H (2007) A novel class of bacteria‐induced small RNAs in Arabidopsis. Genes & Development 21: 3123–3134.

Katiyar‐Agarwal S, Morgan R, Dahlbeck D et al. (2006) A pathogen‐inducible endogenous siRNA in plant immunity. Proceedings of the National Academy of Sciences of the USA 103: 18002–18007.

Kennedy S, Wang D and Ruvkun G (2004) A conserved siRNA‐degrading RNase negatively regulates RNA interference in C. elegans. Nature 427: 645–649.

Kiraly L, Cole AB, Bourque JE and Schoelz JE (1999) Systemic cell death is elicited by the interaction of a single gene in Nicotiana clevelandii and gene VI of Cauliflower mosaic virus. Molecular Plant–Microbe Interaction 12: 919–925.

Kiriakidou M, Tan GS, Lamprinaki S et al. (2007) An mRNA m(7)G cap binding‐like motif within human Ago2 represses translation. Cell 129: 1141–1151.

Kok KH and Jin DY (2006) Influenza A virus NS1 protein does not suppress RNA interference in mammalian cells. Journal of General Virology 87: 2639–2644.

Kon T, Sharma P and Ikegami M (2007) Suppressor of RNA silencing encoded by the monopartite tomato leaf curl Java begomovirus. Archives of Virology 152: 1273–1282.

Kreuze JF, Savenkov EI, Cuellar W, Li XD and Valkonen JPT (2005) Viral class 1 RNase III involved in suppression of RNA silencing. Journal of Virology 79: 7227–7238.

van der Krol AR, Mur LA, Beld M, Mol JN and Stuitje AR (1990) Flavonoid genes in petunia: addition of a limited number of gene copies may lead to a suppression of gene expression. Plant Cell 2: 291–299.

Kubota K, Tsuda S, Tamai A and Meshi T (2003) Tomato mosaic virus replication protein suppresses virus‐targeted posttranscriptional gene silencing. Journal of Virology 77: 11016–11026.

Kurihara Y, Inaba N, Kutsuna N et al. (2007) Binding of tobamovirus replication protein with small RNA duplexes. Journal of General Virology 88: 2347–2352.

Kurihara Y and Watanabe Y (2004) Arabidopsis micro‐RNA biogenesis through dicer‐like 1 protein functions. Proceedings of the National Academy of Sciences of the USA 101: 12753–12758.

Lakatos L, Csorba T, Pantaleo V et al. (2006) Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors. EMBO Journal 25: 2768–2780.

Lakatos L, Szittya G, Silhavy D and Burgyan J (2004) Molecular mechanism of RNA silencing suppression mediated by p19 protein of tombusviruses. EMBO Journal 23: 876–884.

Lecellier C‐H, Dunoyer P, Arar K et al. (2005) A cellular microRNA mediates antiviral defense in human cells. Science 308: 557–560.

Lehner B, Calixto A, Crombie C et al. (2006) Loss of LIN‐35, the Caenorhabditis elegans ortholog of the tumor suppressor p105Rb, results in enhanced RNA interference. Genome Biology 7: R4.

Leuschner PJF, Ameres SL, Kueng S and Martinez J (2006) Cleavage of the siRNA passenger strand during RISC assembly in human cells. EMBO Reports 7: 314–320.

Li F and Ding SW (2006) Virus counterdefense: diverse strategies for evading the RNA‐silencing immunity. Annual Review of Microbiology 60: 503–531.

Li HW and Ding SW (2005) Antiviral silencing in animals. FEBS Letters 579: 5965–5973.

Li HW, Li WX and Ding SW (2002) Induction and suppression of RNA silencing by an animal virus. Science 296: 1319–1321.

Li HW, Lucy AP, Guo HS et al. (1999) Strong host resistance targeted against a viral suppressor of the plant gene silencing defence mechanism. EMBO Journal 18: 2683–2691.

Li WX, Li H, Lu R et al. (2004) Interferon antagonist proteins of influenza and vaccinia viruses are suppressors of RNA silencing. Proceedings of the National Academy of Sciences of the USA 101: 1350–1355.

Lichner Z, Silhavy D and Burgyán J (2003) Double‐stranded RNA‐binding proteins could suppress RNA interference‐mediated antiviral defences. Journal of General Virology 84: 975–980.

Lin J and Cullen BR (2007) Analysis of the interaction of primate retroviruses with the human RNA interference machinery. Journal of Virology 81: 12218–12226.

Lin SS, Wu HW, Jan FJ, Hou RF and Yeh SD (2007) Modifications of the helper component‐protease of Zucchini yellow mosaic virus for generation of attenuated mutants for cross protection against severe infection. Phytopathology 97: 287–296.

Lindbo JA, Silva‐Rosales L, Proebsting WM and Dougherty WG (1993) Induction of a highly specific antiviral state in transgenic plants: implications for regulation of gene expression and virus resistance. Plant Cell 5: 1749–1759.

Lingel A, Simon B, Izaurralde E and Sattler M (2005) The structure of the flock house virus B2 protein, a viral suppressor of RNA interference, shows a novel mode of double‐stranded RNA recognition. EMBO Reports 6: 1149–1155.

Liu H, Reavy B, Swanson M and MacFarlane SA (2002) Functional replacement of the Tobacco rattle virus cysteine‐rich protein by pathogenicity proteins from unrelated plant viruses. Virology 298: 232–239.

Liu J, Carmell MA, Rivas FV et al. (2004a) Argonaute2 is the catalytic engine of mammalian RNAi. Science 305: 1437–1441.

Liu L, Grainger J, Cañizares MC, Angell SM and Lomonossoff GP (2004b) Cowpea mosaic virus RNA‐1 acts as an amplicon whose effects can be counteracted by a RNA‐2‐encoded suppressor of silencing. Virology 323: 37–48.

Liu Q, Rand TA, Kalidas S et al. (2003) R2D2, a bridge between the initiation and effector steps of the Drosophila RNAi pathway. Science 301: 1921–1925.

Liu X, Park JK, Jiang F et al. (2007) Dicer‐1, but not Loquacious, is critical for assembly of miRNA‐induced silencing complexes. RNA 13: 2324–2329.

Lobbes D, Rallapalli G, Schmidt DD, Martin C and Clarke J (2006) SERRATE: a new player on the plant microRNA scene. EMBO Reports 7: 1052–1058.

Love AJ, Laird J, Holt J et al. (2007) Cauliflower mosaic virus protein P6 is a suppressor of RNA silencing. Journal of General Virology 88: 3439–3444.

Lózsa R, Csorba T, Lakatos L and Burgyán J (2008) Inhibition of 3′ modification of small RNAs in virus‐infected plants require spatial and temporal co‐expression of small RNAs and viral silencing‐suppressor proteins. Nucleic Acids Research 36: 4099–4107.

Lu R, Folimonov A, Shintaku M et al. (2004) Three distinct suppressors of RNA silencing encoded by a 20‐kb viral RNA genome. Proceedings of the National Academy of Sciences of the USA 101: 15742–15747.

Lu R, Maduro M, Li F et al. (2005) Animal virus replication and RNAi‐mediated antiviral silencing in Caenorhabditis elegans. Nature 436: 1040–1043.

Lu S and Cullen BR (2004) Adenovirus VA1 noncoding RNA can inhibit small interfering RNA and microRNA biogenesis. Journal of Virology 78: 12868–12876.

Lu YD, Gan QH, Chi XY and Qin S (2008) Roles of microRNA in plant defense and virus offense interaction. Plant Cell Reports.

Lucy AP, Guo HS, Li WX and Ding SW (2000) Suppression of post‐transcriptional gene silencing by a plant viral protein localized in the nucleus. EMBO Journal 19: 1672–1680.

MacDiarmid RM (2005) RNA silencing in productive virus infections. Annual Review of Phytopathology 43: 523–544.

Mallory AC, Ely L, Smith TH et al. (2001) HC‐Pro suppression of transgene silencing eliminates the small RNAs but not transgene methylation or the mobile signal. Plant Cell 13: 571–583.

Marathe R, Smith TH, Anandalakshmi R et al. (2000) Plant viral suppressors of post‐transcriptional silencing do not suppress transcriptional silencing. Plant Journal 22: 51–59.

Martín‐Hernández AM and Baulcombe DC (2008) Tobacco rattle virus 16‐kilodalton protein encodes a suppressor of RNA silencing that allows transient viral entry in meristems. Journal of Virology 82: 4064–4071.

Martínez‐Priego L, Donaire L, Barajas D and Llave C (2008) Silencing suppressor activity of the Tobacco rattle virus‐encoded 16‐kDa protein and interference with endogenous small RNA‐guided regulatory pathways. Virology 376: 346–356.

Martínez‐Turiño S and Hernández C (2009) Inhibition of RNA silencing by the coat protein of Pelargonium flower break virus: distinctions from closely related suppressors. Journal of General Virology 90: 519–525.

Matranga C, Tomari Y, Shin C, Bartel DP and Zamore PD (2005) Passenger‐strand cleavage facilitates assembly of siRNA into Ago2‐containing RNAi enzyme complexes. Cell 123: 607–620.

Meister G, Landthaler M, Patkaniowska A et al. (2004) Human Argonaute2 mediates RNA cleavage targeted by miRNAs and siRNAs. Molecular Cell 15: 185–197.

Meng C, Chen J, Ding SW, Peng J and Wong SM (2008) Hibiscus chlorotic ringspot virus coat protein inhibits trans‐acting small interfering RNA biogenesis in Arabidopsis. Journal of General Virology 89: 2349–2358.

Meng CY, Chen J, Peng JR and Wong SM (2006) Host‐induced avirulence of Hibiscus chlorotic ringspot virus mutants correlates with reduced gene‐silencing suppression activity. Journal of General Virology 87: 451–459.

Mérai Z, Kerényi Z, Kertész S et al. (2006) Double‐stranded RNA binding may be a general plant RNA viral strategy to suppress RNA silencing. Journal of Virology 80: 5747–5756.

Mérai Z, Kerényi Z, Molnár A et al. (2005) Aureusvirus P14 is an efficient RNA silencing suppressor that binds double‐stranded RNAs without size specificity. Journal of Virology 79: 7217–7226.

Mette MF, Matzke AJM and Matzke MA (2001) Resistance of RNA‐mediated TGS to HC‐Pro, a viral suppressor of PTGS, suggests alternative pathways for dsRNA processing. Current Biology 11: 1119–1123.

Mi S, Cai T, Hu Y et al. (2008) Sorting of small RNAs into Arabidopsis argonaute complexes is directed by the 5′ terminal nucleotide. Cell 133: 116–127.

Miyoshi K, Tsukumo H, Nagami T, Siomi H and Siomi MC (2005) Slicer function of Drosophila argonautes and its involvement in RISC formation. Genes & Development 19: 2837–2848.

Mlotshwa S, Pruss GJ, Peragine A et al. (2008a) DICER‐LIKE2 plays a primary role in transitive silencing of transgenes in Arabidopsis. PLoS ONE 3: e1755.

Mlotshwa S, Pruss GJ and Vance V (2008b) Small RNAs in viral infection and host defense. Trends in Plant Science 13: 375–382.

Moissiard G, Parizotto EA, Himber C and Voinnet O (2007) Transitivity in Arabidopsis can be primed, requires the redundant action of the antiviral dicer‐like 4 and dicer‐like 2, and is compromised by viral‐encoded suppressor proteins. RNA 13: 1268–1278.

Moissiard G and Voinnet O (2006) RNA silencing of host transcripts by Cauliflower mosaic virus requires coordinated action of the four Arabidopsis dicer‐like proteins. Proceedings of the National Academy of Sciences of the USA 103: 19593–19598.

Molnár A, Csorba T, Lakatos L et al. (2005) Plant virus‐derived small interfering RNAs originate predominantly from highly structured single‐stranded viral RNAs. Journal of Virology 79: 7812–7818.

Montgomery TA, Howell MD, Cuperus JT et al. (2008) Specificity of ARGONAUTE7‐miR390 interaction and dual functionality in TAS3 trans‐acting siRNA formation. Cell 133: 128–141.

Morel JB, Godon C, Mourrain P et al. (2002) Fertile hypomorphic ARGONAUTE (ago1) mutants impaired in post‐transcriptional gene silencing and virus resistance. Plant Cell 14: 629–639.

Mourrain P, Béclin C, Elmayan T et al. (2000) Arabidopsis SGS2 and SGS3 genes are required for posttranscriptional gene silencing and natural virus resistance. Cell 101: 533–542.

Napoli C, Lemieux C and Jorgensen R (1990) Introduction of a chimeric chalcone synthase gene into petunia results in reversible co‐suppression of homologous genes in trans. Plant Cell 2: 279–289.

Navarro L, Dunoyer P, Jay F et al. (2006) A plant miRNA contributes to antibacterial resistance by repressing auxin signaling. Science 312: 436–439.

Navarro L, Jay F, Nomura K, He SY and Voinnet O (2008) Suppression of the microRNA pathway by bacterial effector proteins. Science 321: 964–967.

Niu QW, Lin SS, Reyes JL et al. (2007) Expression of artificial microRNAs in transgenic Arabidopsis thaliana confers virus resistance. Nature Biotechnology 25: 254–254.

Omarov R, Sparks K, Smith L, Zindovic J and Scholthof HB (2006) Biological relevance of a stable biochemical interaction between the tombusvirus‐encoded p19 and short interfering RNAs. Journal of Virology 80: 3000–3008.

Omarov RT, Ciomperlik JJ and Scholthof HB (2007) RNAi‐associated ssRNA‐specific ribonucleases in Tombusvirus P19 mutant‐infected plants and evidence for a discrete siRNA‐containing effector complex. Proceedings of the National Academy of Sciences of the USA 104: 1714–1719.

Otsuka M, Jing Q, Georgel P et al. (2007) Hypersusceptibility to vesicular stomatitis virus infection in dicer1‐deficient mice is due to impaired miR24 and miR93 expression. Immunity 27: 123–134.

Padgett HS, Watanabe Y and Beachy RN (1997) Identification of the TMV replicase sequence that activates the N gene‐mediated hypersensitive response. Molecular Plant–Microbe Interaction 10: 709–715.

Palauqui JC, Elmayan T, Pollien JM and Vaucheret H (1997) Systemic acquired silencing: transgene‐specific post‐transcriptional silencing is transmitted by grafting from silenced stocks to non‐silenced scions. EMBO Journal 16: 4738–4745.

Pantaleo V and Burgyán J (2008) Cymbidium ringspot virus harnesses RNA silencing to control the accumulation of virus parasite satellite RNA. Journal of Virology 82: 11851–11858.

Pantaleo V, Szittya G and Burgyan J (2007) Molecular bases of viral RNA targeting by viral small interfering RNA‐programmed RISC. Journal of Virology 81: 3797–3806.

Papp I, Mette MF, Aufsatz W et al. (2003) Evidence for nuclear processing of plant microRNA and short interfering RNA precursors. Plant Physiology 132: 1382–1390.

Park W, Li J, Song R, Messing J and Chen X (2002) CARPEL FACTORY, a dicer homolog, and HEN1, a novel protein, act in microRNA metabolism in Arabidopsis thaliana. Current Biology 12: 1484–1495.

Pazhouhandeh M, Dieterle M, Marrocco K et al. (2006) F‐box‐like domain in the polerovirus protein P0 is required for silencing suppressor function. Proceedings of the National Academy of Sciences of the USA 103: 1994–1999.

Pedersen IM, Cheng G, Wieland S et al. (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449: 919–922.

Pfeffer S, Dunoyer P, Heim F et al. (2002) P0 of beet western yellows virus is a suppressor of posttranscriptional gene silencing. Journal of Virology 76: 6815–6824.

Pooggin M and Hohn T (2003) RNAi targeting of DNA virus in plants. Nature Biotechnology 21: 131–132.

Powers JG, Sit TL, Heinsohn C et al. (2008a) The Red clover necrotic mosaic virus RNA‐2 encoded movement protein is a second suppressor of RNA silencing. Virology 381: 277–286.

Powers JG, Sit TL, Qu F et al. (2008b) A versatile assay for the identification of RNA silencing suppressors based on complementation of viral movement. Molecular Plant–Microbe Interactions 21: 879–890.

Preall JB and Sontheimer EJ (2005) RNAi: RISC gets loaded. Cell 123: 543–545.

Pruss G, Ge X, Shi XM, Carrington JC and Vance VB (1997) Plant viral synergism: the potyviral genome encodes a broad‐range pathogenicity enhancer that transactivates replication of heterologous viruses. Plant Cell 9: 859–868.

Pruss GJ, Lawrence CB, Bass T et al. (2004) The potyviral suppressor of RNA silencing confers enhanced resistance to multiple pathogens. Virology 320: 107–120.

Qi Y, He X, Wang XJ et al. (2006) Distinct catalytic and non‐catalytic roles of ARGONAUTE4 in RNA‐directed DNA methylation. Nature 443: 1008–1012.

Qi YJ, Zhong XH, Itaya A and Ding B (2004) Dissecting RNA silencing in protoplasts uncovers novel effects of viral suppressors on the silencing pathway at the cellular level – art. no. e179. Nucleic Acids Research 32: E179.

Qu F, Ren T and Morris TJ (2003) The coat protein of turnip crinkle virus suppresses posttranscriptional gene silencing at an early initiation step. Journal of Virology 77: 511–522.

Qu F, Ye X and Morris TJ (2008) Arabidopsis DRB4, AGO1, AGO7, and RDR6 participate in a DCL4‐initiated antiviral RNA silencing pathway negatively regulated by DCL1. Proceedings of the National Academy of Sciences of the USA 105: 14732–14737.

Qu J, Ye J and Fang R (2007) Artificial microRNA‐mediated virus resistance in plants. Journal of Virology 81: 6690–6699.

Rahim MD, Andika IB, Han C, Kondo H and Tamada T (2007) RNA4‐encoded p31 of beet necrotic yellow vein virus is involved in efficient vector transmission, symptom severity and silencing suppression in roots. Journal of General Virology 88: 1611–1619.

Raja P, Sanville BC, Buchmann RC and Bisaro DM (2008) Viral genome methylation as an epigenetic defense against geminiviruses. Journal of Virology 82: 8997–9007.

Rajagopalan R, Vaucheret H, Trejo J and Bartel DP (2006) A diverse and evolutionarily fluid set of microRNAs in Arabidopsis thaliana. Genes & Development 20: 3407–3425.

Rajamäki ML, Kelloniemi J, Alminaite A et al. (2005) A novel insertion site inside the potyvirus P1 cistron allows expression of heterologous proteins and suggests some P1 functions. Virology 342: 88–101.

Ramachandran V and Chen X (2008) Degradation of microRNAs by a family of exoribonucleases in Arabidopsis. Science 321: 1490–1492.

Rand TA, Ginalski K, Grishin NV and Wang X (2004) Biochemical identification of Argonaute 2 as the sole protein required for RNA‐induced silencing complex activity. Proceedings of the National Academy of Sciences of the USA 101: 14385–14389.

Rand TA, Petersen S, Du F and Wang X (2005) Argonaute2 cleaves the anti‐guide strand of siRNA during RISC activation. Cell 123: 621–629.

Ratcliff F, Harrison BD and Baulcombe DC (1997) A similarity between viral defense and gene silencing in plants. Science 276: 1558–1560.

Reavy B, Dawson S, Canto T and MacFarlane SA (2004) Heterologous expression of plant virus genes that suppress post‐transcriptional gene silencing results in suppression of RNA interference in Drosophila cells. BMC Biotechnology 4: 18.

Reed JC, Kasschau KD, Prokhnevsky AI et al. (2003) Suppressor of RNA silencing encoded by Beet yellows virus. Virology 306: 203–209.

Reinhart BJ, Weinstein EG, Rhoades MW, Bartel B and Bartel DP (2002) MicroRNAs in plants. Genes & Development 16: 1616–1626.

Ren T, Qu F and Morris TJ (2000) HRT gene function requires interaction between a NAC protein and viral capsid protein to confer resistance to Turnip crinkle virus. Plant Cell 12: 1917–1926.

van Rij RP, Saleh MC, Berry B et al. (2006) The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster. Genes & Development 20: 2985–2995.

Rodríguez‐Negrete EA, Carrillo‐Tripp J and Rivera‐Bustamante RF (2009) RNA silencing against geminivirus: complementary action of posttranscriptional gene silencing and transcriptional gene silencing in host recovery. Journal of Virology 83: 1332–1340.

Ruby JG, Jan C, Player C et al. (2006) Large‐scale sequencing reveals 21U‐RNAs and additional microRNAs and endogenous siRNAs in C. elegans. Cell 127: 1193–1207.

Sáenz P, Quiot L, Quiot J‐B, Candresse T and García JA (2001) Pathogenicity determinants in the complex virus population of a Plum pox virus isolate. Molecular Plant–Microbe Interactions 14: 278–287.

Saito K, Nishida KM, Mori T et al. (2006) Specific association of Piwi with rasiRNAs derived from retrotransposon and heterochromatic regions in the Drosophila genome. Genes & Development 20: 2214–2222.

Sarmiento C, Gomez E, Meier M, Kavanagh TA and Truve E (2007) Cocksfoot mottle virus P1 suppresses RNA silencing in Nicotiana benthamiana and Nicotiana tabacum. Virus Research 123: 95–99.

Sarmiento C, Nigul L, Kazantseva J, Buschmann M and Truve E (2006) AtRLI2 is an endogenous suppressor of RNA silencing. Plant Molecular Biology 61: 153–163.

Schnettler E, Hemmes H, Goldbach R and Prins M (2008) The NS3 protein of Rice hoja blanca virus suppresses RNA silencing in mammalian cells. Journal of General Virology 89: 336–340.

Schwach F, Vaistij FE, Jones L and Baulcombe DC (2005) An RNA‐dependent RNA polymerase prevents meristem invasion by Potato virus X and is required for the activity but not the production of a systemic silencing signal. Plant Physiology 138: 1842–1852.

Schwarz DS, Hutvagner G, Du T et al. (2003) Asymmetry in the assembly of the RNAi enzyme complex. Cell 115: 199–208.

Seemanpillai M, Dry I, Randles J and Rezaian A (2003) Transcriptional silencing of geminiviral promoter‐driven transgenes following homologous virus infection. Molecular Plant–Microbe Interactions 16: 429–438.

Segers GC, van Wezel R, Zhang X, Hong Y and Nuss DL (2006) Hypovirus papain‐like protease p29 suppresses RNA silencing in the natural fungal host and in a heterologous plant system. Eukaryotic Cell 5: 896–904.

Segers GC, Zhang X, Deng F, Sun Q and Nuss DL (2007) Evidence that RNA silencing functions as an antiviral defense mechanism in fungi. Proceedings of the National Academy of Sciences of the USA 104: 12902–12906.

Senda M, Masuta C, Ohnishi S et al. (2004) Patterning of virus‐infected Glycine max seed coat is associated with suppression of endogenous silencing of chalcone synthase genes. Plant Cell 16: 807–818.

Shiboleth YM, Haronsky E, Leibman D et al. (2007) The conserved FRNK box in HC‐Pro, a plant viral suppressor of gene silencing, is required for small RNA binding and mediates symptom development. Journal of Virology 81: 13135–13148.

Shivaprasad PV, Rajeswaran R, Blevins T et al. (2008) The CaMV transactivator/viroplasmin interferes with RDR6‐dependent trans‐acting and secondary siRNA pathways in Arabidopsis. Nucleic Acids Research 36: 5896–5909.

Silhavy D, Molnár A, Lucioli A et al. (2002) A viral protein suppresses RNA silencing and binds silencing‐generated, 21‐ to 25‐nucleotide double‐stranded RNAs. EMBO Journal 21: 3070–3080.

Simmer F, Tijsterman M, Parrish S et al. (2002) Loss of the putative RNA‐directed RNA polymerase RRF‐3 makes C. elegans hypersensitive to RNAi. Current Biology 12: 1317–1319.

Simón‐Mateo C and García JA (2006) MicroRNA‐guided processing impairs Plum pox virus replication, but the virus readily evolves to escape this silencing mechanism. Journal of Virology 80: 2429–2436.

Singh DP, Moore CA, Gilliland A and Carr JP (2004) Activation of multiple antiviral defence mechanisms by salicylic acid. Molecular Plant Pathology 5: 57–63.

Smith LM, Pontes O, Searle I et al. (2007) An SNF2 protein associated with nuclear RNA silencing and the spread of a silencing signal between cells in Arabidopsis. Plant Cell 19: 1507–1521.

Soldan SS, Plassmeyer ML, Matukonis MK and González‐Scarano F (2005) La Crosse virus nonstructural protein NSs counteracts the effects of short interfering RNA. Journal of Virology 79: 234–244.

Souret FF, Kastenmayer JP and Green PJ (2004) AtXRN4 degrades mRNA in Arabidopsis and its substrates include selected miRNA targets. Molecular Cell 15: 173–183.

Steiner FA, Hoogstrate SW, Okihara KL et al. (2007) Structural features of small RNA precursors determine Argonaute loading in Caenorhabditis elegans. Nature Structural & Molecular Biology 14: 927–933.

Sullivan CS and Ganem D (2005a) A virus‐encoded inhibitor that blocks RNA interference in mammalian cells. Journal of Virology 79: 7371–7379.

Sullivan CS and Ganem D (2005b) MicroRNAs and viral infection. Molecular Cell 20: 3–7.

Sunter G and Bisaro DM (1992) Transactivation of geminivirus AR1 and BR1 gene expression by the viral AL2 gene product occurs at the level of transcription. Plant Cell 4: 1321–1331.

Susi P, Hohkuri M, Wahlroos T and Kilby NJ (2004) Characteristics of RNA silencing in plants: similarities and differences across kingdoms. Plant Molecular Biology 54: 157–174.

Suzuki N, Chen B and Nuss DL (1999) Mapping of a hypovirus p29 protease symptom determinant domain with sequence similarity to potyvirus HC‐Pro protease. Journal of Virology 73: 9478–9484.

Takeda A, Iwasaki S, Watanabe T, Utsumi M and Watanabe Y (2008) The mechanism selecting the guide strand from small RNA duplexes is different among Argonaute proteins. Plant and Cell Physiology 49: 493–500.

Takeda A, Sugiyama K, Nagano H et al. (2002) Identification of a novel RNA silencing suppressor, NSs protein of Tomato spotted wilt virus. FEBS Letters 532: 75–79.

Takeda A, Tsukuda M, Mizumoto H et al. (2005) A plant RNA virus suppresses RNA silencing through viral RNA replication. EMBO Journal 24: 3147–3157.

Taliansky M, Roberts IM, Kalinina N et al. (2003) An umbraviral protein, involved in long‐distance RNA movement, binds viral RNA and forms unique, protective ribonucleoprotein complexes. Journal of Virology 77: 3031–3040.

Tang G, Reinhart BJ, Bartel DP and Zamore PD (2003) A biochemical framework for RNA silencing in plants. Genes & Development 17: 49–63.

Te J, Melcher U, Howard A and Verchot‐Lubicz J (2005) Soilborne wheat mosaic virus (SBWMV) 19 K protein belongs to a class of cysteine rich proteins that suppress RNA silencing. Virology Journal 2: 18.

Tenllado F, Barajas D, Vargas M et al. (2003) Transient expression of homologous hairpin RNA causes interference with plant virus infection and is overcome by a virus encoded suppressor of gene silencing. Molecular Plant–Microbe Interactions 16: 149–158.

Thomas CL, Leh V, Lederer C and Maule AJ (2003) Turnip crinkle virus coat protein mediates suppression of RNA silencing in Nicotiana benthamiana. Virology 306: 33–41.

Till S, Lejeune E, Thermann R et al. (2007) A conserved motif in Argonaute‐interacting proteins mediates functional interactions through the Argonaute PIWI domain. Nature Structural & Molecular Biology 14: 897–903.

Tolia NH and Joshua‐Tor L (2007) Slicer and the Argonautes. Nature Chemical Biology 3: 36–43.

Tomari Y, Du T and Zamore PD (2007) Sorting of Drosophila small silencing RNAs. Cell 130: 299–308.

Tomari Y, Matranga C, Haley B, Martinez N and Zamore PD (2004) A protein sensor for siRNA asymmetry. Science 306: 1377–1380.

Torres‐Barceló C, Martín S, Daròs JA and Elena SF (2008) From hypo‐ to hyper‐suppression: effect of amino acid substitutions on the RNA silencing suppressor activity of tobacco etch virus HC‐Pro. Genetics, Epub ahead of print, PMID: 18780745.

Triboulet R, Mari B, Lin YL et al. (2007) Suppression of microRNA‐silencing pathway by HIV‐1 during virus replication. Science 315: 1579–1582.

Trinks D, Rajeswaran R, Shivaprasad PV et al. (2005) Suppression of RNA silencing by a geminivirus nuclear protein, AC2, correlates with transactivation of host genes. Journal of Virology 79: 2517–2527.

Tsuda S, Kubota K, Kanda A, Ohki T and Meshi T (2007) Pathogenicity of Pepper mild mottle virus is controlled by the RNA silencing suppression activity of its replication protein but not the viral accumulation. Phytopathology 97: 412–420.

Valli A, Dujovny G and García JA (2008) Protease activity, self interaction, and small interfering RNA binding of the silencing suppressor P1b from Cucumber vein yellowing ipomovirus. Journal of Virology 82: 974–986.

Valli A, López‐Moya JJ and García JA (2007) Recombination and gene duplication in the evolutionary diversification of P1 proteins in the family Potyviridae. Journal of General Virology 88: 1016–1028.

Valli A, Martín‐Hernández AM, López‐Moya JJ and García JA (2006) RNA silencing suppression by a second copy of the P1 serine protease of Cucumber vein yellowing ipomovirus (CVYV), a member of the family Potyviridae that lacks the cysteine protease HCPro. Journal of Virology 80: 10055–10063.

Vanderschuren H, Akbergenov R, Pooggin MM et al. (2007) Transgenic cassava resistance to African cassava mosaic virus is enhanced by viral DNA‐A bidirectional promoter‐derived siRNAs. Plant Molecular Biology 64: 549–557.

Vanitharani R, Chellappan P, Pita JS and Fauquet CM (2004) Differential roles of AC2 and AC4 of cassava geminiviruses in mediating synergism and suppression of posttranscriptional gene silencing. Journal of Virology 78: 9487–9498.

Vargason JM, Szittya G, Burgyan J and Tanaka Hall TM (2003) Size selective recognition of siRNA by an RNA silencing suppressor. Cell 115: 799–811.

Vasudevan S, Tong Y and Steitz JA (2007) Switching from repression to activation: microRNAs can up‐regulate translation. Science 318: 1931–1934.

Vaucheret H (2006) Post‐transcriptional small RNA pathways in plants: mechanisms and regulations. Genes & Development 20: 759–771.

Vaucheret H (2008) Plant ARGONAUTES. Trends in Plant Science 13: 350–358.

Vaucheret H, Vazquez F, Crete P and Bartel DP (2004) The action of ARGONAUTE1 in the miRNA pathway and its regulation by the miRNA pathway are crucial for plant development. Genes & Development 18: 1187–1197.

Vazquez F, Gasciolli V, Crete P and Vaucheret H (2004) The nuclear dsRNA binding protein HYL1 Is required for microRNA accumulation and plant development, but not posttranscriptional transgene silencing. Current Biology 14: 346–351.

Verdel A, Jia S, Gerber S et al. (2004) RNAi‐mediated targeting of heterochromatin by the RITS complex. Science 303: 672–676.

Vogler H, Akbergenov R, Shivaprasad PV et al. (2007) Modification of small RNAs associated with suppression of RNA silencing by tobamovirus replicase protein. Journal of Virology 81: 10379–10288.

Vogler H, Kwon MO, Dang V et al. (2008) Tobacco mosaic virus movement protein enhances the spread of RNA silencing. PLoS Pathogens 4: e1000038.

Voinnet O (2001) RNA silencing as a plant immune system against viruses. Trends in Genetics 17: 449–459.

Voinnet O and Baulcombe DC (1997) Systemic signalling in gene silencing. Nature 389: 553.

Voinnet O, Lederer C and Baulcombe DC (2000) A viral movement protein prevents spread of the gene silencing signal in Nicotiana benthamiana. Cell 103: 157–167.

Voinnet O, Pinto YM and Baulcombe DC (1999) Suppression of gene silencing: a general strategy used by diverse DNA and RNA viruses of plants. Proceedings of the National Academy of Sciences of the USA 96: 14147–14152.

de Vries W and Berkhout B (2008) RNAi suppressors encoded by pathogenic human viruses. International Journal of Biochemistry & Cell Biology 40: 2007–2012.

Wang H, Buckley KJ, Yang XJ, Buchmann RC and Bisaro DM (2005) Adenosine kinase inhibition and suppression of RNA silencing by geminivirus AL2 and L2 proteins. Journal of Virology 79: 7410–7418.

Wang H, Hao L, Shung CY, Sunter G and Bisaro DM (2003) Adenosine kinase is inactivated by geminivirus AL2 and L2 proteins. Plant Cell 15: 3020–3032.

Wang MB, Bian XY, Wu LM et al. (2004a) On the role of RNA silencing in the pathogenicity and evolution of viroids and viral satellites. Proceedings of the National Academy of Sciences of the USA 101: 3275–3280.

Wang XH, Aliyari R, Li WX et al. (2006a) RNA interference directs innate immunity against viruses in adult Drosophila. Science 312: 452–454.

Wang Y, Kato N, Jazag A et al. (2006b) Hepatitis C virus core protein is a potent inhibitor of RNA silencing‐based antiviral response. Gastroenterology 130: 883–892.

Wang YZ, Tzfira T, Gaba V et al. (2004b) Functional analysis of the Cucumber mosaic virus 2b protein: pathogenicity and nuclear localization. Journal of General Virology 85: 3135–3147.

van Wezel R, Dong XL, Liu HT et al. (2002) Mutation of three cysteine residues in Tomato yellow leaf curl virus‐China C2 protein causes dysfunction in pathogenesis and posttranscriptional gene‐silencing suppression. Molecular Plant–Microbe Interactions 15: 203–208.

Whitham SA and Wang YZ (2004) Roles for host factors in plant viral pathogenicity. Current Opinion in Plant Biology 7: 365–371.

Xie Z, Allen E, Wilken A and Carrington JC (2005) DICER‐LIKE 4 functions in trans‐acting small interfering RNA biogenesis and vegetative phase change in Arabidopsis thaliana. Proceedings of the National Academy of Sciences of the USA 102: 12984–12989.

Xie Z, Johansen LK, Gustafson AM et al. (2004) Genetic and functional diversification of small RNA pathways in plants. PLoS Biology 2: 1–11.

Xie ZX, Fan BF, Chen CH and Chen ZX (2001) An important role of an inducible RNA‐dependent RNA polymerase in plant antiviral defense. Proceedings of the National Academy of Sciences of the USA 98: 6516–6521.

Xu N, Segerman B, Zhou X and Akusjarvi G (2007) Adenovirus virus‐associated RNAII‐derived small RNAs are efficiently incorporated into the RNA‐induced silencing complex and associate with polyribosomes. Journal of Virology 81: 10540–10549.

Yaegashi H, Takahashi T, Isogai M et al. (2007a) Apple chlorotic leaf spot virus 50 kDa movement protein acts as a suppressor of systemic silencing without interfering with local silencing in Nicotiana benthamiana. Journal of General Virology 88: 316–324.

Yaegashi H, Tamura A, Isogai M and Yoshikawa N (2008) Inhibition of long‐distance movement of RNA silencing signals in Nicotiona benthamiana by Apple chlorotic leaf spot virus 50 kDa movement protein. Virology 382: 199–206.

Yaegashi H, Yamatsuta T, Takahashi T et al. (2007b) Characterization of virus‐induced gene silencing in tobacco plants infected with apple latent spherical virus. Archives of Virology 152: 1839–1849.

Yang L, Liu Z, Lu F, Dong A and Huang H (2006) SERRATE is a novel nuclear regulator in primary microRNA processing in Arabidopsis. Plant Journal 47: 841–850.

Ye K, Malinina L and Patel DJ (2003) Recognition of small interfering RNA by a viral suppressor of RNA silencing. Nature 426: 874–878.

Ye KQ and Patel DJ (2005) RNA silencing suppressor p21 of Beet yellows virus forms an RNA binding octameric ring structure. Structure 13: 1375–1384.

Yelina NE, Savenkov EI, Solovyev AG, Morozov SY and Valkonen JP (2002) Long‐distance movement, virulence, and RNA silencing suppression controlled by a single protein in Hordei‐ and Potyviruses: complementary functions between virus families. Journal of Virology 76: 12981–12991.

Yi H and Richards EJ (2007) A cluster of disease resistance genes in Arabidopsis is coordinately regulated by transcriptional activation and RNA silencing. Plant Cell 19: 2929–2939.

Yoshikawa M, Peragine A, Park MY and Poethig RS (2005) A pathway for the biogenesis of trans‐acting siRNAs in Arabidopsis. Genes & Development 19: 2164–2175.

Yu B, Bi L, Zheng B et al. (2008) The FHA domain proteins DAWDLE in Arabidopsis and SNIP1 in humans act in small RNA biogenesis. Proceedings of the National Academy of Sciences of the USA 105: 10073–10078.

Yu B, Chapman EJ, Yang Z, Carrington JC and Chen X (2006) Transgenically expressed viral RNA silencing suppressors interfere with microRNA methylation in Arabidopsis. FEBS Letters 580: 3117–3120.

Yu B, Yang ZY, Li JJ et al. (2005) Methylation as a crucial step in plant microRNA biogenesis. Science 307: 932–935.

Yu D, Fan B, MacFarlane SA and Chen Z (2003) Analysis of the involvement of an inducible Arabidopsis RNA‐dependent RNA polymerase in antiviral defense. Molecular Plant–Microbe Interactions 16: 206–216.

Zhang X, Du P, Lu L et al. (2008a) Contrasting effects of HC‐Pro and 2b viral suppressors from Sugarcane mosaic virus and Tomato aspermy cucumovirus on the accumulation of siRNAs. Virology 374: 351–360.

Zhang X, Yuan Y‐R, Pei Y et al. (2006) Cucumber mosaic virus‐encoded 2b suppressor inhibits Arabidopsis Argonaute1 cleavage activity to counter plant defense. Genes & Development 20: 3255–3268.

Zhang XM, Segers GC, Sun QH, Deng FY and Nuss DL (2008b) Characterization of hypovirus‐derived small RNAs generated in the chestnut blight fungus by an inducible DCL‐2‐dependent pathway. Journal of Virology 82: 2613–2619.

Zheng X, Zhu J, Kapoor A and Zhu JK (2007) Role of Arabidopsis AGO6 in siRNA accumulation, DNA methylation and transcriptional gene silencing. EMBO Journal 26: 1691–1701.

Zhou Z, Dell'orco M, Saldarelli P et al. (2006) Identification of an RNA‐silencing suppressor in the genome of Grapevine virus A. Journal of General Virology 87: 2387–2395.

Zilberman D, Cao X and Jacobsen SE (2003) ARGONAUTE4 control of locus‐specific siRNA accumulation and DNA and histone methylation. Science 299: 716–719.

Zrachya A, Glick E, Levy Y et al. (2007) Suppressor of RNA silencing encoded by Tomato yellow leaf curl virus‐Israel. Virology 358: 159–165.

Further Reading

Baulcombe D (2004) RNA silencing in plants. Nature 431: 356–363.

Eamens A, Wang MB, Smith NA and Waterhouse PM (2008) RNA silencing in plants: Yesterday, today, and tomorrow. Plant Physiology 147: 456–468.

Moissiard G and Voinnet O (2004) Viral suppression of RNA silencing in plants. Molecular Plant Pathology 5: 71–82.

Qu F and Morris TJ (2005) Suppressors of RNA silencing encoded by plant viruses and their role in viral infections. FEBS Letters 579: 5958–5964.

Roth BM, Pruss GJ and Vance VB (2004) Plant viral suppressors of RNA silencing. Virus Research 102: 97–108.

Voinnet O (2008) Post‐transcriptional RNA silencing in plant‐microbe interactions: a touch of robustness and versatility. Current Opinion in Plant Biology 11: 464–470.

Xie Q and Guo HS (2006) Systemic antiviral silencing in plants. Virus Research 118: 1–6.

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Valli, Adrián, López‐Moya, Juan José, and García, Juan Antonio(Sep 2009) RNA Silencing and its Suppressors in the Plant‐virus Interplay. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0021261]