Identification and Characterization of a Novel Non-Structural Protein of Bluetongue Virus

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Bluetongue virus (BTV) is the causative agent of a major disease of livestock (bluetongue). For over two decades, it has been widely accepted that the 10 segments of the dsRNA genome of BTV encode for 7 structural and 3 non-structural proteins. The non-structural proteins (NS1, NS2, NS3/NS3a) play different key roles during the viral replication cycle. In this study we show that BTV expresses a fourth non-structural protein (that we designated NS4) encoded by an open reading frame in segment 9 overlapping the open reading frame encoding VP6. NS4 is 77–79 amino acid residues in length and highly conserved among several BTV serotypes/strains. NS4 was expressed early post-infection and localized in the nucleoli of BTV infected cells. By reverse genetics, we showed that NS4 is dispensable for BTV replication in vitro, both in mammalian and insect cells, and does not affect viral virulence in murine models of bluetongue infection. Interestingly, NS4 conferred a replication advantage to BTV-8, but not to BTV-1, in cells in an interferon (IFN)-induced antiviral state. However, the BTV-1 NS4 conferred a replication advantage both to a BTV-8 reassortant containing the entire segment 9 of BTV-1 and to a BTV-8 mutant with the NS4 identical to the homologous BTV-1 protein. Collectively, this study suggests that NS4 plays an important role in virus-host interaction and is one of the mechanisms played, at least by BTV-8, to counteract the antiviral response of the host. In addition, the distinct nucleolar localization of NS4, being expressed by a virus that replicates exclusively in the cytoplasm, offers new avenues to investigate the multiple roles played by the nucleolus in the biology of the cell.

Vyšlo v časopise: Identification and Characterization of a Novel Non-Structural Protein of Bluetongue Virus. PLoS Pathog 7(12): e32767. doi:10.1371/journal.ppat.1002477
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1002477

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1. MellorPSBaylisMMertensPP 2009 Bluetongue; Pastoret P-P, editor. London Academic Press

2. MaclachlanNJDrewCPDarpelKEWorwaG 2009 The pathology and pathogenesis of bluetongue. J Comp Pathol 141 1 16

3. Schwartz-CornilIMertensPPContrerasVHematiBPascaleF 2008 Bluetongue virus: virology, pathogenesis and immunity. Vet Res 39 46

4. ErasmusBJPotgieterAC 2009 The history of blueotngue. MellorPSBaylisMMertensP Bluetongue Amsterdam Elsevier 7 21

5. MaclachlanNJGuthrieAJ 2010 Re-emergence of bluetongue, African horse sickness, and other Orbivirus diseases. Vet Res 41 35

6. WilsonAJMellorPS 2009 Bluetongue in Europe: past, present and future. Philos Trans R Soc Lond B Biol Sci 364 2669 2681

7. GrimesJMBurroughsJNGouetPDiproseJMMalbyR 1998 The atomic structure of the bluetongue virus core. Nature 395 470 478

8. NasonELRothagelRMukherjeeSKKarAKForzanM 2004 Interactions between the inner and outer capsids of bluetongue virus. J Virol 78 8059 8067

9. GouetPDiproseJMGrimesJMMalbyRBurroughsJN 1999 The highly ordered double-stranded RNA genome of bluetongue virus revealed by crystallography. Cell 97 481 490

10. RoyP 2008 Functional mapping of bluetongue virus proteins and their interactions with host proteins during virus replication. Cell Biochem Biophys 50 143 157

11. ZhangXBoyceMBhattacharyaBZhangXScheinS 2011 Bluetongue virus coat protein VP2 contains sialic acid-binding domains, and VP5 resembles enveloped virus fusion proteins. Proc Natl Acad Sci U S A 107 6292 6297

12. HofmannMARenzulloSMaderMChaignatVWorwaG 2008 Genetic characterization of toggenburg orbivirus, a new bluetongue virus, from goats, Switzerland. Emerg Infect Dis 14 1855 1861

13. MaanSMaanNSSamuelARRaoSAttouiH 2007 Analysis and phylogenetic comparisons of full-length VP2 genes of the 24 bluetongue virus serotypes. J Gen Virol 88 621 630

14. DeMaulaCDBonneauKRMacLachlanNJ 2000 Changes in the outer capsid proteins of bluetongue virus serotype ten that abrogate neutralization by monoclonal antibodies. Virus Res 67 59 66

15. MertensPPDiproseJ 2004 The bluetongue virus core: a nano-scale transcription machine. Virus Res 101 29 43

16. StauberNMartinez-CostasJSuttonGMonastyrskayaKRoyP 1997 Bluetongue virus VP6 protein binds ATP and exhibits an RNA-dependent ATPase function and a helicase activity that catalyze the unwinding of double-stranded RNA substrates. J Virol 71 7220 7226

17. SuttonGGrimesJMStuartDIRoyP 2007 Bluetongue virus VP4 is an RNA-capping assembly line. Nat Struct Mol Biol 14 449 451

18. RoyP 2008 Bluetongue virus: dissection of the polymerase complex. J Gen Virol 89 1789 1804

19. NoadRRoyP 2009 Bluetongue virus replication and assembly. MellorPBaylisMMertensP Bluetongue Amsterdam Academic Press 53 76

20. BoyceMWehrfritzJNoadRRoyP 2004 Purified recombinant bluetongue virus VP1 exhibits RNA replicase activity. J Virol 78 3994 4002

21. WehrfritzJMBoyceMMirzaSRoyP 2007 Reconstitution of bluetongue virus polymerase activity from isolated domains based on a three-dimensional structural model. Biopolymers 86 83 94

22. OwensRJLimnCRoyP 2004 Role of an arbovirus nonstructural protein in cellular pathogenesis and virus release. J Virol 78 6649 6656

23. HorscroftNJRoyP 2000 NTP binding and phosphohydrolase activity associated with purified bluetongue virus non-structural protein NS2. J Gen Virol 81 1961 1965

24. CelmaCCRoyP 2009 A viral nonstructural protein regulates bluetongue virus trafficking and release. J Virol 83 6806 6816

25. HanZHartyRN 2004 The NS3 protein of bluetongue virus exhibits viroporin-like properties. J Biol Chem 279 43092 43097

26. BoyceMCelmaCCRoyP 2008 Development of reverse genetics systems for bluetongue virus: recovery of infectious virus from synthetic RNA transcripts. J Virol 82 8339 8348

27. MertensPPBrownFSangarDV 1984 Assignment of the genome segments of bluetongue virus type 1 to the proteins which they encode. Virology 135 207 217

28. Van DijkAAHuismansH 1988 In vitro transcription and translation of bluetongue virus mRNA. J Gen Virol 69 Pt 3 573 581

29. FirthAE 2008 Bioinformatic analysis suggests that the Orbivirus VP6 cistron encodes an overlapping gene. Virol J 5 48

30. ArnaudFBlackSGMurphyLGriffithsDJNeilSJ 2010 Interplay between ovine bone marrow stromal cell antigen 2/tetherin and endogenous retroviruses. J Virol 84 4415 4425

31. WechslerSJMcHollandLETabachnickWJ 1989 Cell lines from Culicoides variipennis (Diptera: Ceratopogonidae) support replication of bluetongue virus. J Invertebr Pathol 54 385 393

32. MatsuoERoyP 2009 Bluetongue virus VP6 acts early in the replication cycle and can form the basis of chimeric virus formation. J Virol 83 8842 8848

33. MaanSMaanNSRoss-smithNBattenCAShawAE 2008 Sequence analysis of bluetongue virus serotype 8 from the Netherlands 2006 and comparison to other European strains. Virology 377 308 318

34. DulbeccoRVogtM 1953 Some problems of animal virology as studied by the plaque technique. Cold Spring Harb Symp Quant Biol 18 273 279

35. Van HeekeGOttTLStraussAAmmaturoDBazerFW 1996 High yield expression and secretion of the ovine pregnancy recognition hormone interferon-tau by Pichia pastoris. J Interferon Cytokine Res 16 119 126

36. ReedLJMuenchHA 1938 A simple method for estimating fifty percent endpoints. Am J Hyg 27 493 497

37. VarelaMChowYHSturkieCMurciaPPalmariniM 2006 Association of RON tyrosine kinase with the Jaagsiekte sheep retrovirus envelope glycoprotein. Virology 350 347 357

38. PalmariniMSharpJMDe las HerasMFanH 1999 Jaagsiekte sheep retrovirus is necessary and sufficient to induce a contagious lung cancer in sheep. Journal Virol 73 6964 6972

39. MuraMMurciaPCaporaleMSpencerTENagashimaK 2004 Late viral interference induced by transdominant Gag of an endogenous retrovirus. Proc Natl Acad Sci U S A 101 11117 11122

40. LindstromMS 2011 NPM1/B23: A multifunctional chaperone in ribosome biogenesis and chromatin remodeling. Biochem Res Int 2011 195209

41. MarforiMMynottAEllisJJMehdiAMSaundersNF 2011 Molecular basis for specificity of nuclear import and prediction of nuclear localization. Biochim Biophys Acta 1813 1562 1577

42. FosterNMLuedkeAJParsonsonIMWaltonTE 1991 Temporal relationships of viremia, interferon activity, and antibody responses of sheep infected with several bluetongue virus strains. Am J Vet Res 52 192 196

43. MacLachlanNJThompsonJ 1985 Bluetongue virus-induced interferon in cattle. Am J Vet Res 46 1238 1241

44. RinaldoCRJrOverallJCJrGlasgowLA 1975 Viral replication and interferon production in fetal and adult ovine leukocytes and spleen cells. Infect Immun 12 1070 1077

45. BazerFWSpencerTEOttTL 1997 Interferon tau: a novel pregnancy recognition signal. Am J Reprod Immunol 37 412 420

46. Calvo-PinillaERodriguez-CalvoTAnguitaJSevillaNOrtegoJ 2009 Establishment of a bluetongue virus infection model in mice that are deficient in the alpha/beta interferon receptor. PLoS One 4 e5171

47. FranchiPMercanteMTRonchiGFArmillottaGUlisseS 2008 Laboratory tests for evaluating the level of attenuation of bluetongue virus. J Virol Methods 153 263 265

48. Calvo-PinillaENietoJMOrtegoJ 2010 Experimental oral infection of bluetongue virus serotype 8 in IFNAR(-/-) mice. J Gen Virol 91 2821 2825

49. CaporaleMWashRPiniASaviniGFranchiP 2011 Determinants of bluetongue virus virulence in murine models of disease. J Virol 85 11479 11489

50. FirthAEAtkinsJF 2010 Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame overlapping genes accessed by leaky scanning. Virol J 7 17

51. BoisvertFMvan KoningsbruggenSNavascuesJLamondAI 2007 The multifunctional nucleolus. Nat Rev Mol Cell Biol 8 574 585

52. BoulonSWestmanBJHuttenSBoisvertFMLamondAI 2010 The nucleolus under stress. Mol Cell 40 216 227

53. HiscoxJA 2007 RNA viruses: hijacking the dynamic nucleolus. Nat Rev Microbiol 5 119 127

54. BrandtSBlissenbachMGreweBKonietznyRGrunwaldT 2007 Rev proteins of human and simian immunodeficiency virus enhance RNA encapsidation. PLoS Pathog 3 e54

55. CaporaleMArnaudFMuraMGolderMMurgiaC 2009 The signal peptide of a simple retrovirus envelope functions as a posttranscriptional regulator of viral gene expression. J Virol 83 4591 4604

56. MalimMHHauberJLeSYMaizelJVCullenBR 1989 The HIV-1 rev trans-activator acts through a structured target sequence to activate nuclear export of unspliced viral mRNA. Nature 338 254 257

57. MertzJALozanoMMDudleyJP 2009 Rev and Rex proteins of human complex retroviruses function with the MMTV Rem-responsive element. Retrovirology 6 10

58. NevilleMStutzFLeeLDavisLIRosbashM 1997 The importin-beta family member Crm1p bridges the interaction between Rev and the nuclear pore complex during nuclear export. Curr Biol 7 767 775

59. HiscoxJAWurmTWilsonLBrittonPCavanaghD 2001 The coronavirus infectious bronchitis virus nucleoprotein localizes to the nucleolus. J Virol 75 506 512

60. LeeCHodginsDCalvertJGWelchSKJolieR 2006 Mutations within the nuclear localization signal of the porcine reproductive and respiratory syndrome virus nucleocapsid protein attenuate virus replication. Virology 346 238 250

61. PeeplesMEWangCGuptaKCColemanN 1992 Nuclear entry and nucleolar localization of the Newcastle disease virus (NDV) matrix protein occur early in infection and do not require other NDV proteins. J Virol 66 3263 3269

62. MichelMRElgizoliMDaiYJakobRKobletH 1990 Karyophilic properties of Semliki Forest virus nucleocapsid protein. J Virol 64 5123 5131

63. WangSHSyuWJHuangKJLeiHYYaoCW 2002 Intracellular localization and determination of a nuclear localization signal of the core protein of dengue virus. J Gen Virol 83 3093 3102

64. YangMRLeeSROhWLeeEWYehJY 2008 West Nile virus capsid protein induces p53-mediated apoptosis via the sequestration of HDM2 to the nucleolus. Cell Microbiol 10 165 176

65. VolmerRMazel-SanchezBVolmerCSoubiesSMGuerinJL 2010 Nucleolar localization of influenza A NS1: striking differences between mammalian and avian cells. Virol J 7 63

66. Vazquez-IglesiasLLostale-SeijoIMartinez-CostasJBenaventeJ 2009 Avian reovirus sigmaA localizes to the nucleolus and enters the nucleus by a nonclassical energy- and carrier-independent pathway. J Virol 83 10163 10175

67. AminevAGAminevaSPPalmenbergAC 2003 Encephalomyocarditis virus (EMCV) proteins 2A and 3BCD localize to nuclei and inhibit cellular mRNA transcription but not rRNA transcription. Virus Res 95 59 73

68. AminevAGAminevaSPPalmenbergAC 2003 Encephalomyocarditis viral protein 2A localizes to nucleoli and inhibits cap-dependent mRNA translation. Virus Res 95 45 57

69. Gonzalez-LopezCMartinez-CostasJEstebanMBenaventeJ 2003 Evidence that avian reovirus sigmaA protein is an inhibitor of the double-stranded RNA-dependent protein kinase. J Gen Virol 84 1629 1639

70. VinsonCMyakishevMAcharyaAMirAAMollJR 2002 Classification of human B-ZIP proteins based on dimerization properties. Mol Cell Biol 22 6321 6335

71. EstesMK 2001 Rotaviruses and their replication. KnipeDMHowleyPM Virology Philadelphia Lippincott, Williams and Wilkins 1747 1786

72. RainsfordEWMcCraeMA 2007 Characterization of the NSP6 protein product of rotavirus gene 11. Virus Res 130 193 201

73. JamesonPSchoenherrCKGrossbergSE 1978 Bluetongue virus, an exceptionally potent interferon inducer in mice. Infect Immun 20 321 323

74. RandallREGoodbournS 2008 Interferons and viruses: an interplay between induction, signalling, antiviral responses and virus countermeasures. J Gen Virol 89 1 47

75. ArnoldMMPattonJT 2011 Diversity of interferon antagonist activities mediated by NSP1 proteins of different rotavirus strains. J Virol 85 1970 1979

76. BarroMPattonJT 2005 Rotavirus nonstructural protein 1 subverts innate immune response by inducing degradation of IFN regulatory factor 3. Proc Natl Acad Sci U S A 102 4114 4119

77. FengNSenAWolfMVoPHoshinoY 2011 Roles of VP4 and NSP1 in determining the distinctive replication capacities of simian rotavirus RRV and bovine rotavirus UK in the mouse biliary tract. J Virol 85 2686 2694

78. SherryB 2009 Rotavirus and reovirus modulation of the interferon response. J Interferon Cytokine Res 29 559 567

79. RojasMAriasCFLopezS 2010 Protein kinase R is responsible for the phosphorylation of eIF2alpha in rotavirus infection. J Virol 84 10457 10466

80. GrimmDStaeheliPHufbauerMKoernerIMartinez-SobridoL 2007 Replication fitness determines high virulence of influenza A virus in mice carrying functional Mx1 resistance gene. Proc Natl Acad Sci U S A 104 6806 6811