1887

Journal of General Virology header logo

Volume 96, Issue 11

Characterization of a second open reading frame in genome segment 10 of bluetongue virus Open Access

Abstract

Viruses have often evolved overlapping reading frames in order to maximize their coding capacity. Until recently, the segmented dsRNA genome of viruses of the genus was thought to be monocistronic, but the identification of the bluetongue virus (BTV) NS4 protein changed this assumption. A small ORF in segment 10, overlapping the NS3 ORF in the +1 position, is maintained in more than 300 strains of the 27 different BTV serotypes and in more than 200 strains of the phylogenetically related African horse sickness virus (AHSV). In BTV, this ORF (named S10-ORF2 in this study) encodes a putative protein 50–59 residues in length and appears to be under strong positive selection. HA- or GFP-tagged versions of S10-ORF2 expressed from transfected plasmids localized within the nucleoli of transfected cells, unless a putative nucleolar localization signal was mutated. S10-ORF2 inhibited gene expression, but not RNA translation, in transient transfection reporter assays. In both mammalian and insect cells, BTV S10-ORF2 deletion mutants (BTV8ΔS10-ORF2) displayed similar replication kinetics to wt virus. , S10-ORF2 deletion mutants were pathogenic in mouse models of disease. Although further evidence is required for S10-ORF2 expression during infection, the data presented provide an initial characterization of this ORF.

  • Received:
  • Accepted:
  • Published Online:
© 2015 The Authors
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000267
2015-11-01
2024-04-19
Loading full text...

Full text loading...

/deliver/fulltext/jgv/96/11/3280.html?itemId=/content/journal/jgv/10.1099/jgv.0.000267&mimeType=html&fmt=ahah

References

  1. Aminev A.G., Amineva S.P., Palmenberg A.C. 2003; Encephalomyocarditis viral protein 2A localizes to nucleoli and inhibits cap-dependent mRNA translation. Virus Res 95:45–57 [View Article][PubMed]
     [Google Scholar]
  2. Arnaud F., Black S.G., Murphy L., Griffiths D.J., Neil S.J., Spencer T.E., Palmarini M. 2010; Interplay between ovine bone marrow stromal cell antigen 2/tetherin and endogenous retroviruses. J Virol 84:4415–4425 [View Article][PubMed]
     [Google Scholar]
  3. Barratt-Boyes S.M., MacLachlan N.J. 1995; Pathogenesis of bluetongue virus infection of cattle. J Am Vet Med Assoc 206:1322–1329[PubMed]
     [Google Scholar]
  4. Bazzini A.A., Johnstone T.G., Christiano R., Mackowiak S.D., Obermayer B., Fleming E.S., Vejnar C.E., Lee M.T., Rajewsky N., other authors. 2014; Identification of small ORFs in vertebrates using ribosome footprinting and evolutionary conservation. EMBO J 33:981–993 [View Article][PubMed]
     [Google Scholar]
  5. Beaton A.R., Rodriguez J., Reddy Y.K., Roy P. 2002; The membrane trafficking protein calpactin forms a complex with bluetongue virus protein NS3 and mediates virus release. Proc Natl Acad Sci U S A 99:13154–13159 [View Article][PubMed]
     [Google Scholar]
  6. Belhouchet M., Mohd Jaafar F., Firth A.E., Grimes J.M., Mertens P.P., Attoui H. 2011; Detection of a fourth orbivirus non-structural protein. PLoS One 6:e25697 [View Article][PubMed]
     [Google Scholar]
  7. Belli B.A., Samuel C.E. 1993; Biosynthesis of reovirus-specified polypeptides: identification of regions of the bicistronic reovirus S1 mRNA that affect the efficiency of translation in animal cells. Virology 193:16–27 [View Article][PubMed]
     [Google Scholar]
  8. Boyce M., Celma C.C., Roy P. 2008; Development of reverse genetics systems for bluetongue virus: recovery of infectious virus from synthetic RNA transcripts. J Virol 82:8339–8348 [View Article][PubMed]
     [Google Scholar]
  9. Boyce M., Celma C.C., Roy P. 2012; Bluetongue virus non-structural protein 1 is a positive regulator of viral protein synthesis. Virol J 9:178 [View Article][PubMed]
     [Google Scholar]
  10. Burger K., Eick D. 2013; Functional ribosome biogenesis is a prerequisite for p53 destabilization: impact of chemotherapy on nucleolar functions and RNA metabolism. Biol Chem 394:1133–1143 [View Article][PubMed]
     [Google Scholar]
  11. Butan C., Tucker P. 2010; Insights into the role of the non-structural protein 2 (NS2) in bluetongue virus morphogenesis. Virus Res 151:109–117 [View Article][PubMed]
     [Google Scholar]
  12. Calvo-Pinilla E., Rodríguez-Calvo T., Anguita J., Sevilla N., Ortego J. 2009; Establishment of a bluetongue virus infection model in mice that are deficient in the alpha/beta interferon receptor. PLoS One 4:e5171 [View Article][PubMed]
     [Google Scholar]
  13. Caporale M., Arnaud F., Mura M., Golder M., Murgia C., Palmarini M. 2009; The signal peptide of a simple retrovirus envelope functions as a posttranscriptional regulator of viral gene expression. J Virol 83:4591–4604 [View Article][PubMed]
     [Google Scholar]
  14. Caporale M., Wash R., Pini A., Savini G., Franchi P., Golder M., Patterson-Kane J., Mertens P., Di Gialleonardo L., other authors. 2011; Determinants of bluetongue virus virulence in murine models of disease. J Virol 85:11479–11489 [View Article][PubMed]
     [Google Scholar]
  15. Caporale M., Di Gialleonorado L., Janowicz A., Wilkie G., Shaw A., Savini G., Van Rijn P.A., Mertens P., Di Ventura M., Palmarini M. 2014; Virus and host factors affecting the clinical outcome of bluetongue virus infection. J Virol 88:10399–10411 [View Article][PubMed]
     [Google Scholar]
  16. Celma C.C., Roy P. 2009; A viral nonstructural protein regulates bluetongue virus trafficking and release. J Virol 83:6806–6816 [View Article][PubMed]
     [Google Scholar]
  17. Chauveau E., Doceul V., Lara E., Adam M., Breard E., Sailleau C., Viarouge C., Desprat A., Meyer G., other authors. 2012; Sensing and control of bluetongue virus infection in epithelial cells via RIG-I and MDA5 helicases. J Virol 86:11789–11799 [View Article][PubMed]
     [Google Scholar]
  18. Chauveau E., Doceul V., Lara E., Breard E., Sailleau C., Vidalain P.O., Meurs E.F., Dabo S., Schwartz-Cornil I., other authors. 2013; NS3 of bluetongue virus interferes with the induction of type I interferon. J Virol 87:8241–8246 [View Article][PubMed]
     [Google Scholar]
  19. Coetzee P., Stokstad M., Myrmel M., Mutowembwa P., Loken T., Venter E.H., Van Vuuren M. 2013; Transplacental infection in goats experimentally infected with a European strain of bluetongue virus serotype 8. Vet J 197:335–341 [View Article][PubMed]
     [Google Scholar]
  20. Darpel K.E., Batten C.A., Veronesi E., Shaw A.E., Anthony S., Bachanek-Bankowska K., Kgosana L., bin-Tarif A., Carpenter S., other authors. 2007; Clinical signs and pathology shown by British sheep and cattle infected with bluetongue virus serotype 8 derived from the 2006 outbreak in northern Europe. Vet Rec 161:253–261 [View Article][PubMed]
     [Google Scholar]
  21. Dercksen D., Groot Nibbelink N., Paauwe R., Backx A., van Rijn P., Vellema P. 2007; [First outbreak of bluetongue in goats in The Netherlands]. Tijdschr Diergeneeskd 132:786–790 (in Dutch)
    [Google Scholar]
  22. Doceul V., Chauveau E., Lara E., Bréard E., Sailleau C., Zientara S., Vitour D. 2014; Dual modulation of type I interferon response by bluetongue virus. J Virol 88:10792–10802 [View Article][PubMed]
     [Google Scholar]
  23. Edgar R.C. 2004; muscle: multiple sequence alignment with high accuracy and high throughput. Nucleic Acids Res 32:1792–1797 [View Article][PubMed]
     [Google Scholar]
  24. Elbers A.R., Backx A., Meroc E., Gerbier G., Staubach C., Hendrickx G., van der Spek A., Mintiens K. 2008a; Field observations during the bluetongue serotype 8 epidemic in 2006. I. Detection of first outbreaks and clinical signs in sheep and cattle in Belgium, France and the Netherlands. Prev Vet Med 87:21–30 [View Article][PubMed]
     [Google Scholar]
  25. Elbers A.R., Backx A., Mintiens K., Gerbier G., Staubach C., Hendrickx G., van der Spek A. 2008b; Field observations during the bluetongue serotype 8 epidemic in 2006. II. Morbidity and mortality rate, case fatality and clinical recovery in sheep and cattle in the Netherlands. Prev Vet Med 87:31–40 [View Article][PubMed]
     [Google Scholar]
  26. Emmott E., Hiscox J.A. 2009; Nucleolar targeting: the hub of the matter. EMBO Rep 10:231–238 [View Article][PubMed]
     [Google Scholar]
  27. Farley K.I., Surovtseva Y., Merkel J., Baserga S.J. 2015; Determinants of mammalian nucleolar architecture. Chromosoma 124:323–331[PubMed] [CrossRef]
     [Google Scholar]
  28. Firth A.E. 2008; Bioinformatic analysis suggests that the Orbivirus VP6 cistron encodes an overlapping gene. Virol J 5:48 [View Article][PubMed]
     [Google Scholar]
  29. Firth A.E., Brierley I. 2012; Non-canonical translation in RNA viruses. J Gen Virol 93:1385–1409 [View Article][PubMed]
     [Google Scholar]
  30. Franchi P., Mercante M.T., Ronchi G.F., Armillotta G., Ulisse S., Molini U., Di Ventura M., Lelli R., Savini G., Pini A. 2008; Laboratory tests for evaluating the level of attenuation of bluetongue virus. J Virol Methods 153:263–265 [View Article][PubMed]
     [Google Scholar]
  31. Gouet P., Diprose J.M., Grimes J.M., Malby R., Burroughs J.N., Zientara S., Stuart D.I., Mertens P.P. 1999; The highly ordered double-stranded RNA genome of bluetongue virus revealed by crystallography. Cell 97:481–490 [View Article][PubMed]
     [Google Scholar]
  32. Grimes J.M., Burroughs J.N., Gouet P., Diprose J.M., Malby R., Ziéntara S., Mertens P.P., Stuart D.I. 1998; The atomic structure of the bluetongue virus core. Nature 395:470–478 [View Article][PubMed]
     [Google Scholar]
  33. Guzmán F.A., Distéfano A.J., Arneodo J.D., Hopp H.E., Lenardon S.L., del Vas M., Conci L.R. 2007; Sequencing of the bicistronic genome segments S7 and S9 of Mal de Río Cuarto virus (Fijivirus, Reoviridae) completes the genome of this virus. Arch Virol 152:565–573 [View Article][PubMed]
     [Google Scholar]
  34. Henrich M., Reinacher M., Hamann H.P. 2007; Lethal bluetongue virus infection in an alpaca. Vet Rec 161:764 [View Article][PubMed]
     [Google Scholar]
  35. Hughes A.L., Hughes M.A. 2005; Patterns of nucleotide difference in overlapping and non-overlapping reading frames of papillomavirus genomes. Virus Res 113:81–88 [View Article][PubMed]
     [Google Scholar]
  36. Hughes A.L., Westover K., da Silva J., O'Connor D.H., Watkins D.I. 2001; Simultaneous positive and purifying selection on overlapping reading frames of the tat and vpr genes of simian immunodeficiency virus. J Virol 75:7966–7972 [View Article][PubMed]
     [Google Scholar]
  37. Huismans H., Erasmus B.J. 1981; Identification of the serotype-specific and group-specific antigens of bluetongue virus. Onderstepoort J Vet Res 48:51–58[PubMed]
     [Google Scholar]
  38. Jaber T., Yuan Y. 2013; A virally encoded small peptide regulates RTA stability and facilitates Kaposi's sarcoma-associated herpesvirus lytic replication. J Virol 87:3461–3470 [View Article][PubMed]
     [Google Scholar]
  39. Janowicz A., Caporale M., Shaw A., Gulletta S., Di Gialleonardo L., Ratinier M., Palmarini M. 2015; Multiple genome segments determine virulence of bluetongue virus serotype 8. J Virol 89:5238–5249 [View Article][PubMed]
     [Google Scholar]
  40. Jenckel M., Bréard E., Schulz C., Sailleau C., Viarouge C., Hoffmann B., Höper D., Beer M., Zientara S. 2015; Complete coding genome sequence of putative novel bluetongue virus serotype 27. Genome Announc 3:e00016–e00015 [View Article][PubMed]
     [Google Scholar]
  41. Kahlon J., Sugiyama K., Roy P. 1983; Molecular basis of bluetongue virus neutralization. J Virol 48:627–632[PubMed]
     [Google Scholar]
  42. Kar A.K., Bhattacharya B., Roy P. 2007; Bluetongue virus RNA binding protein NS2 is a modulator of viral replication and assembly. BMC Mol Biol 8:4 [View Article][PubMed]
     [Google Scholar]
  43. Katoh K., Kuma K., Toh H., Miyata T. 2005; mafft version 5: improvement in accuracy of multiple sequence alignment. Nucleic Acids Res 33:511–518 [View Article][PubMed]
     [Google Scholar]
  44. Kosakovsky Pond S.L., Frost S.D. 2005; Not so different after all: a comparison of methods for detecting amino acid sites under selection. Mol Biol Evol 22:1208–1222 [CrossRef]
     [Google Scholar]
  45. Lam Y.W., Trinkle-Mulcahy L. 2015; New insights into nucleolar structure and function. F1000Prime Rep 7:48 [View Article][PubMed]
     [Google Scholar]
  46. Lymperopoulos K., Noad R., Tosi S., Nethisinghe S., Brierley I., Roy P. 2006; Specific binding of bluetongue virus NS2 to different viral plus-strand RNAs. Virology 353:17–26 [View Article][PubMed]
     [Google Scholar]
  47. Maclachlan N.J., Drew C.P., Darpel K.E., Worwa G. 2009; The pathology and pathogenesis of bluetongue. J Comp Pathol 141:1–16 [View Article][PubMed]
     [Google Scholar]
  48. Mauroy A., Guyot H., De Clercq K., Cassart D., Thiry E., Saegerman C. 2008; Bluetongue in captive yaks. Emerg Infect Dis 14:675–676 [View Article][PubMed]
     [Google Scholar]
  49. Mellor P.S., Baylis M., Mertens P.P. 2009 Bluetongue London: Academic Press;
     [Google Scholar]
  50. Meyer G., Lacroux C., Léger S., Top S., Goyeau K., Deplanche M., Lemaire M. 2009; Lethal bluetongue virus serotype 1 infection in llamas. Emerg Infect Dis 15:608–610 [View Article][PubMed]
     [Google Scholar]
  51. Mohan K.V., Atreya C.D. 2001; Nucleotide sequence analysis of rotavirus gene 11 from two tissue culture-adapted ATCC strains, RRV and Wa. Virus Genes 23:321–329 [View Article][PubMed]
     [Google Scholar]
  52. Monastyrskaya K., Gould E.A., Roy P. 1995; Characterization and modification of the carboxy-terminal sequences of bluetongue virus type 10 NS1 protein in relation to tubule formation and location of an antigenic epitope in the vicinity of the carboxy terminus of the protein. J Virol 69:2831–2841[PubMed]
     [Google Scholar]
  53. Murrell B., Moola S., Mabona A., Weighill T., Sheward D., Kosakovsky Pond S.L., Scheffler K. 2013; FUBAR: a fast, unconstrained Bayesian approximation for inferring selection. Mol Biol Evol 30:1196–1205 [View Article][PubMed]
     [Google Scholar]
  54. Owens R.J., Limn C., Roy P. 2004; Role of an arbovirus nonstructural protein in cellular pathogenesis and virus release. J Virol 78:6649–6656 [View Article][PubMed]
     [Google Scholar]
  55. Palmarini M., Datta S., Omid R., Murgia C., Fan H. 2000; The long terminal repeat of Jaagsiekte sheep retrovirus is preferentially active in differentiated epithelial cells of the lungs. J Virol 74:5776–5787 [View Article][PubMed]
     [Google Scholar]
  56. Pond S.L., Frost S.D. 2005; Datamonkey: rapid detection of selective pressure on individual sites of codon alignments. Bioinformatics 21:2531–2533 [View Article][PubMed]
     [Google Scholar]
  57. Racine T., Barry C., Roy K., Dawe S.J., Shmulevitz M., Duncan R. 2007; Leaky scanning and scanning-independent ribosome migration on the tricistronic S1 mRNA of avian reovirus. J Biol Chem 282:25613–25622 [View Article][PubMed]
     [Google Scholar]
  58. Ratinier M., Caporale M., Golder M., Franzoni G., Allan K., Nunes S.F., Armezzani A., Bayoumy A., Rixon F., other authors. 2011; Identification and characterization of a novel non-structural protein of bluetongue virus. PLoS Pathog 7:e1002477 [View Article][PubMed]
     [Google Scholar]
  59. Rawlinson S.M., Moseley G.W. 2015; The nucleolar interface of RNA viruses. Cell Microbiol 17:1108–1120 [View Article][PubMed]
     [Google Scholar]
  60. Roy P. 2008; Bluetongue virus: dissection of the polymerase complex. J Gen Virol 89:1789–1804 [View Article][PubMed]
     [Google Scholar]
  61. Roy P., Noad R. 2006; Bluetongue virus assembly and morphogenesis. Curr Top Microbiol Immunol 309:87–116[PubMed]
     [Google Scholar]
  62. Scott M.S., Troshin P.V., Barton G.J. 2011; NoD: a nucleolar localization sequence detector for eukaryotic and viral proteins. BMC Bioinformatics 12:317 [View Article][PubMed]
     [Google Scholar]
  63. Sealfon R.S., Lin M.F., Jungreis I., Wolf M.Y., Kellis M., Sabeti P.C. 2015; FRESCo: finding regions of excess synonymous constraint in diverse viruses. Genome Biol 16:38 [View Article][PubMed]
     [Google Scholar]
  64. Shaw A.E., Ratinier M., Nunes S.F., Nomikou K., Caporale M., Golder M., Allan K., Hamers C., Hudelet P., other authors. 2013; Reassortment between two serologically unrelated bluetongue virus strains is flexible and can involve any genome segment. J Virol 87:543–557 [View Article][PubMed]
     [Google Scholar]
  65. Slavoff S.A., Mitchell A.J., Schwaid A.G., Cabili M.N., Ma J., Levin J.Z., Karger A.D., Budnik B.A., Rinn J.L., Saghatelian A. 2013; Peptidomic discovery of short open reading frame-encoded peptides in human cells. Nat Chem Biol 9:59–64 [View Article][PubMed]
     [Google Scholar]
  66. Stamatakis A. 2014; RAxML version 8: a tool for phylogenetic analysis and post-analysis of large phylogenies. Bioinformatics 30:1312–1313 [View Article][PubMed]
     [Google Scholar]
  67. Storz G., Wolf Y.I., Ramamurthi K.S. 2014; Small proteins can no longer be ignored. Annu Rev Biochem 83:753–777 [View Article][PubMed]
     [Google Scholar]
  68. Suzuki N., Sugawara M., Nuss D.L., Matsuura Y. 1996; Polycistronic (tri- or bicistronic) phytoreoviral segments translatable in both plant and insect cells. J Virol 70:8155–8159[PubMed]
     [Google Scholar]
  69. Varela M., Schnettler E., Caporale M., Murgia C., Barry G., McFarlane M., McGregor E., Piras I.M., Shaw A., other authors. 2013; Schmallenberg virus pathogenesis, tropism and interaction with the innate immune system of the host. PLoS Pathog 9:e1003133 [View Article][PubMed]
     [Google Scholar]
  70. Versteeg G.A., Rajsbaum R., Sánchez-Aparicio M.T., Maestre A.M., Valdiviezo J., Shi M., Inn K.S., Fernandez-Sesma A., Jung J., García-Sastre A. 2013; The E3-ligase TRIM family of proteins regulates signaling pathways triggered by innate immune pattern-recognition receptors. Immunity 38:384–398 [View Article][PubMed]
     [Google Scholar]
  71. Vitour D., Doceul V., Ruscanu S., Chauveau E., Schwartz-Cornil I., Zientara S. 2014; Induction and control of the type I interferon pathway by bluetongue virus. Virus Res 182:59–70 [View Article][PubMed]
     [Google Scholar]
  72. Voon K., Chua K.B., Yu M., Crameri G., Barr J.A., Malik Y., Wang L.F. 2011; Evolutionary relationship of the L- and M-class genome segments of bat-borne fusogenic orthoreoviruses in Malaysia and Australia. J Gen Virol 92:2930–2936 [View Article][PubMed]
     [Google Scholar]
  73. Wechsler S.J., McHolland L.E., Tabachnick W.J. 1989; Cell lines from Culicoides variipennis (Diptera: Ceratopogonidae) support replication of bluetongue virus. J Invertebr Pathol 54:385–393 [View Article][PubMed]
     [Google Scholar]
  74. Yoneyama M., Suhara W., Fukuhara Y., Sato M., Ozato K., Fujita T. 1996; Autocrine amplification of type I interferon gene expression mediated by interferon stimulated gene factor 3 (ISGF3). J Biochem 120:160–169 [View Article][PubMed]
     [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000267
Loading
Characterization of a second open reading frame in genome segment 10 of bluetongue virus
J. Gen. Virol. 96, 3280 (2015); https://doi.org/10.1099/jgv.0.000267
/content/journal/jgv/10.1099/jgv.0.000267
/content/journal/jgv/10.1099/jgv.0.000267
Loading

Data & Media loading...

Most cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error