39. Ji J, Glaser A, Wernli M, Berke JM, Moradpour D, et al. (2008) Suppression of short interfering RNA-mediated gene silencing by the structural proteins of hepatitis C virus. J Gen Virol 89: 2761–2766. 40. Karjee S, Minhas A, Sood V, Ponia SS, Banerjea AC, et al. (2011) The 7a accessory protein of severe acute respiratory syndrome coronavirus acts as an RNA silencing suppressor. J Virol 84: 10395–10401. 41. Jing XL, Fan MN, Jia G, Liu LW, Ma L, et al. (2011) A multifunctional protein encoded by Turkey herpesvirus suppresses RNA silencing in Nicotiana benthamiana. J Virol 85: 12792–12803. 42. Bivalkar-Mehla S, Vakharia J, Mehla R, Abreha M, Kanwar JR, et al. (2011) Viral RNA silencing suppressors (RSS): novel strategy of viruses to ablate the host RNA interference (RNAi) defense system. Virus Res 155: 1–9. 43. Li HW, Ding SW (2005) Antiviral silencing in animals. FEBS Lett 579: 5965– 5973. 44. Wu Q, Wang X, Ding SW (2010) Viral suppressors of RNA-based viral immunity: host targets. Cell Host Microbe 8: 12–15. 45. de Vries W, Berkhout B (2008) RNAi suppressors encoded by pathogenic human viruses. Internat J Biochem Cell Biol 40: 2007–2012. 46. Haasnoot J, Westerhout EM, Berkhout B (2007) RNA interference against viruses: strike and counterstrike. Nat Biotechnol 25: 1435–1443. 47. Delmas B, Kibenge FSB, Leong JC, Mundt E, Vakaharia VN, et al. (2004) Family Birnaviridae. In: Fauquet CM, Mayo MA, Maniloff J, Desselberger U, Bal LA, editors. Virus Taxonomy, VIII Report of the ICTV. London: Elsevier/Academic Press. 561–569. 48. van den Berg TP, Eterradossi N, Toquin D, Meulemans G (2000) Infectious bursal disease (Gumboro disease). Rev Sci Tech 19: 509–543. 49. Go´ mez-Casado E, Estepa A, Coll JM (2011) A comparative review on European-farmed finfish RNA viruses and their vaccines. Vaccine 29: 2657– 2671. 50. Luque D, Rivas G, Alfonso C, Carrascosa JL, Rodriguez JF, et al. (2009) Infectious bursal disease virus is an icosahedral polyploid dsRNA virus. Proc Natl Acad Sci USA 106: 2148–2152. 51. Birghan C, Mundt E, Gorbalenya AE (2000) A non-canonical lon proteinase lacking the ATPase domain employs the ser-Lys catalytic dyad to exercise broad control over the life cycle of a double-stranded RNA virus. EMBO J 19: 114–123. 52. Maraver A, Ona A, Abaitua F, Gonzalez D, Clemente R, et al. (2003) The oligomerization domain of VP3, the scaffolding protein of infectious bursal disease virus, plays a critical role in capsid assembly. J Virol 77: 6438–6449. 53. Saugar I, Irigoyen N, Luque D, Carrascosa JL, Rodriguez JF, et al. (2010) Electrostatic interactions between capsid and scaffolding proteins mediate the structural polymorphism of a double-stranded RNA virus. J Biol Chem 285: 3643–3650. 54. Garriga D, Navarro A, Querol-Audi J, Abaitua F, Rodriguez JF, et al. (2007) Activation mechanism of a noncanonical RNA-dependent RNA polymerase. Proc Natl Acad Sci USA 104: 20540–20545. 55. Luque D, Saugar I, Rejas MT, Carrascosa JL, Rodriguez JF, et al. (2009) Infectious bursal disease virus: ribonucleoprotein complexes of a double- stranded RNA virus. J Mol Biol 386: 891–901. 56. Casa n˜as A, Navarro A, Ferrer-Orta C, Gonza´lez D, Rodr´ıguez JF, et al. (2008) Structural insights into the multifunctional protein VP3 of birnaviruses. Structure 16: 29–37. 57. Reinisch KM (2002) The dsRNA Viridae and their catalytic capsids. Nat Struct Mol Biol 9: 714–716. 58. Harrison SC (2007) Principles of virus structure. In: Knipe DM, Howley PM, Griffin DE, Lamb RA, Martin MA, et al., editors. Fields Virology. Philadelphia: Lippincott Williams & Wilkins. 59–98. 59. Coulibaly F, Chevalier C, Gutsche I, Pous J, Navaza J, et al. (2005) The birnavirus crystal structure reveals structural relationships among icosahedral viruses. Cell 120: 761–772. 60. Saugar I, Luque D, Ona A, Rodriguez JF, Carrascosa JL, et al. (2005) Structural polymorphism of the major capsid protein of a double-stranded RNA virus: an amphipathic alpha helix as a molecular switch. Structure 13: 1007–1017. 61. Bridge AJ, Pebernard S, Ducraux A, Nicoulaz AL, Iggo R (2003) Induction of an interferon response by RNAi vectors in mammalian cells. Nat Genet 34: 263–264. 62. Sledz CA, Holko M, De Veer MJ, Silverman RH, Williams BR (2003) Activation of the interferon system by short-interfering RNAs. Nat Cell Biol 5: 834–839. 63. Valli A, Dujovny G, Garc´ıa JA (2008) Protease activity, self interaction, and small interfering RNA binding of the silencing suppressor P1b from Cucumber vein yellowing ipomovirus. J Virol 82: 974–986. 64. Valli A, Oliveros JC, Molnar A, Baulcombe D, Garc´ıa JA (2011) The specific binding to 21-nt double-stranded RNAs is crucial for the anti-silencing activity of Cucumber vein yellowing virus P1b and perturbs endogenous small RNA populations. RNA 17: 1148–1158. 65. Tacken MG, Peeters BP, Thomas AA, Rottier PJ, Boot HJ (2002) Infectious bursal disease virus capsid protein VP3 interacts both with VP1, the RNA- dependent RNA polymerase, and with viral double-stranded RNA. J Virol 76: 11301–11311. 66. Kochan G, Gonzalez D, Rodriguez JF (2003) Characterization of the RNA- binding activity of VP3, a major structural protein of Infectious bursal disease virus. Arch Virol 148: 723–744. VP3 Proteins Suppress RNA Silencing 67. Pedersen T, Skjesol A, Jorgensen JB (2007) VP3, a structural protein of infectious pancreatic necrosis virus, interacts with RNA-dependent RNA polymerase VP1 and with double-stranded RNA. J Virol 81: 6652–6663. 68. Carrington JC, Cary SM, Parks TD, Dougherty WG (1989) A second proteinase encoded by a plant potyvirus genome. EMBO J 8: 365–370. 69. Qian S, Zhong X, Yu L, Ding B, de Haan P, et al. (2009) HIV-1 Tat RNA silencing suppressor activity is conserved across kingdoms and counteracts translational repression of HIV-1. Proc Natl Acad Sci USA 106: 605–610. 70. Me´rai Z, Kere´nyi Z, Kerte´sz S, Magna M, Lakatos L, et al. (2006) Double- stranded RNA binding may be a general plant RNA viral strategy to suppress RNA silencing. J Virol 80: 5747–5756. 71. Chao JA, Lee JH, Chapados BR, Debler EW, Schneemann A, et al. (2005) Dual modes of RNA-silencing suppression by flock house virus protein B2. Nat Struct Mol Biol 12: 952–957. 72. van Rij RP, Saleh MC, Berry B, Foo C, Houk A, et al. (2006) The RNA silencing endonuclease Argonaute 2 mediates specific antiviral immunity in Drosophila melanogaster. Genes Dev 20: 2985–2995. 73. Schnettler E, Hemmes H, Huismann R, Goldbach R, Prins M, et al. (2010) Diverging affinity of tospovirus RNA silencing suppressor proteins, NSs, for various RNA duplex molecules. J Virol 84: 11542–11554. 74. Fenner BJ, Goh W, Kwang J (2006) Sequestration and protection of double- stranded RNA by the betanodavirus B2 protein. J Virol 80: 6822–6833. 75. Hemmes H, Lakatos L, Goldbach R, Burgyan J, 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. 76. Lakatos L, Csorba T, Pantaleo V, Chapman EJ, Carrington JC, et al. (2006) Small RNA binding is a common strategy to suppress RNA silencing by several viral suppressors. EMBO J 25: 2768–2780. 77. Vargason JM, Szittya G, Burgyan J, Tanaka Hall TM (2003) Size selective recognition of siRNA by an RNA silencing suppressor. Cell 115: 799–811. 78. Ye K, Malinina L, Patel DJ (2003) Recognition of small interfering RNA by a viral suppressor of RNA silencing. Nature 426: 874–878. 79. Lingel A, Simon B, Izaurralde E, 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 Rep 6: 1149–1155. 80. Carbonell A, Dujovny G, Garcia JA, Valli A (2012) The Cucumber vein yellowing virus silencing suppressor P1b can functionally replace HCPro in Plum pox virus infection in a host-specific manner. Mol Plant-Microbe Interact 25: 151–164. 81. Garcia-Ruiz H, Takeda A, Chapman EJ, Sullivan CM, Fahlgren N, et al. (2010) Arabidopsis RNA-dependent RNA polymerases and dicer-like proteins in antiviral defense and small interfering RNA biogenesis during Turnip mosaic virus infection. Plant Cell 22: 481–496. 82. Maliogka V, Calvo M, Carbonell AT, Garcia JA, Valli AA (2012) Heterologous RNA silencing suppressors from both plant- and animal-infecting viruses support Plum pox virus infection. J Gen Virol 93: 1601–1611. 83. Lu R, Maduro M, Li F, Li HW, Broitman-Maduro G, et al. (2005) Animal virus replication and RNAi-mediated antiviral silencing in Caenorhabditis elegans. Nature 436: 1040–1043. 84. Han YH, Luo YJ, Wu Q, Jovel J, Wang XH, et al. (2011) RNA-based immunity terminates viral infection in adult Drosophila in absence of viral suppression of RNAi: Characterization of viral siRNA populations in wildtype and mutant flies. J Virol 85: 13153–13163. 85. Blair CD (2011) Mosquito RNAi is the major innate immune pathway controlling arbovirus infection and transmission. Future Microbiol 6: 265–277. 86. Zambon RA, Vakharia VN, Wu LP (2006) RNAi is an antiviral immune response against a dsRNA virus in Drosophila melanogaster. Cell Microbiol 8: 880–889. 87. Fenner BJ, Thiagarajan R, Chua HK, Kwang J (2006) Betanodavirus B2 is an RNA interference antagonist that facilitates intracellular viral RNA accumu- lation. J Virol 80: 85–94. 88. Iwamoto T, Mise K, Takeda A, Okinaka Y, Mori K, et al. (2005) Characterization of Striped jack nervous necrosis virus subgenomic RNA3 and biological activities of its encoded protein B2. J Gen Virol 86: 2807–2816. 89. Cullen BR (2006) Is RNA interference involved in intrinsic antiviral immunity in mammals? Nat Immunol 7: 563–567. 90. Gottwein E, Mukherjee N, Sachse C, Frenzel C, Majoros WH, et al. (2007) A viral microRNA functions as an orthologue of cellular miR-155. Nature 450: 1096–U1017. 91. Gupta A, Gartner JJ, Sethupathy P, Hatzigeorgiou AG, Fraser NW (2006) Anti-apoptotic function of a microRNA encoded by the HSV-1 latency- associated transcript. Nature 442: 82–85. 92. Huang J, Wang F, Argyris E, Chen K, Liang Z, et al. (2007) Cellular microRNAs contribute to HIV-1 latency in resting primary CD4+ T lymphocytes. Nat Med 13: 1241–1247. 93. Otsuka M, Jing Q, Georgel P, New L, Chen J, 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. 94. Pedersen IM, Cheng G, Wieland S, Volinia S, Croce CM, et al. (2007) Interferon modulation of cellular microRNAs as an antiviral mechanism. Nature 449: 919–922. 95. Song L, Liu H, Gao S, Jiang W, Huang W (2010) Cellular microRNAs inhibit replication of the H1N1 influenza A virus in infected cells. J Virol 84: 8849– 8860. PLOS ONE | www.plosone.org 11 September 2012 | Volume 7 | Issue 9 | e45957