1887

Abstract

The process by which eukaryotic viruses with segmented genomes select a complete set of genome segments for packaging into progeny virus particles is not understood. In this study a model based on the association of genome segments through specific RNA–RNA interactions driven by base pairing was formalized and tested in the genus of the family. A strategy combining screening of the genomic sequences for inter-segment complementarity with direct functional testing of inter-segment RNA–RNA interactions using reverse genetics is described in the type species of the genus, (BTV). Two examples, involving four of the ten BTV genomic segments, of specific inter-segment interaction motifs whose maintenance is essential for the generation of infectious virus, were identified. Equivalent inter-segment complementarities were found between the identified regions of the orthologous genome segments of all orbiviruses, including phylogenetically distant species. Specific interaction of the participating RNA segments was confirmed using electrophoretic mobility shift assays, with the interactions inhibited using oligonucleotides complementary to the interaction motif of one of the interacting partners, and also through mutagenesis of the motifs. In each example, the base pairing rather than the absolute sequence was critical to the formation of a functional inter-segment interaction, with mutations only being tolerated in rescued virus if compensating changes were made in the interacting partner to restore uninterrupted base pairing. The absolute sequence of the complementarity motifs varied between species, indicating that this newly identified phenomenon may contribute to the observed lack of reassortment between species.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.000400
2016-05-01
2024-04-18
Loading full text...

Full text loading...

/deliver/fulltext/jgv/97/5/1145.html?itemId=/content/journal/jgv/10.1099/jgv.0.000400&mimeType=html&fmt=ahah

References

  1. Ballard A., McCrae M. A., Desselberger U. 1992; Nucleotide sequences of normal and rearranged RNA segments 10 of human rotaviruses. J Gen Virol 73:633–638 [View Article][PubMed]
    [Google Scholar]
  2. Boyce M., McCrae M. A. 2015; Rapid mapping of functional cis-acting RNA elements by recovery of virus from a degenerate RNA population: application to genome segment 10 of bluetongue virus. J Gen Virol 96:3072–3082 [View Article][PubMed]
    [Google Scholar]
  3. 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]
  4. 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]
  5. Brooke C. B., Ince W. L., Wrammert J., Ahmed R., Wilson P. C., Bennink J. R., Yewdell J. W. 2013; Most influenza A virions fail to express at least one essential viral protein. J Virol 87:3155–3162 [View Article][PubMed]
    [Google Scholar]
  6. Burkhardt C., Sung P. Y., Celma C. C., Roy P. 2014; Structural constraints in the packaging of bluetongue virus genomic segments. J Gen Virol 95:2240–2250 [View Article][PubMed]
    [Google Scholar]
  7. Capra J. A., Singh M. 2007; Predicting functionally important residues from sequence conservation. Bioinformatics 23:1875–1882 [View Article][PubMed]
    [Google Scholar]
  8. Crick F. H. 1966; Codon–anticodon pairing: the wobble hypothesis. J Mol Biol 19:548–555 [View Article][PubMed]
    [Google Scholar]
  9. Essere B., Yver M., Gavazzi C., Terrier O., Isel C., Fournier E., Giroux F., Textoris J., Julien T. other authors 2013; Critical role of segment-specific packaging signals in genetic reassortment of influenza A viruses. Proc Natl Acad Sci U S A 110:E3840–E3848 [View Article][PubMed]
    [Google Scholar]
  10. Feenstra F., van Gennip R. G., Maris-Veldhuis M., Verheij E., van Rijn P. A. 2014; Bluetongue virus without NS3/NS3a expression is not virulent and protects against virulent BTV challenge. J Gen Virol 95:2019–2029 [View Article]
    [Google Scholar]
  11. Gault E., Schnepf N., Poncet D., Servant A., Teran S., Garbarg-Chenon A. 2001; A human rotavirus with rearranged genes 7 and 11 encodes a modified NSP3 protein and suggests an additional mechanism for gene rearrangement. J Virol 75:7305–7314 [View Article][PubMed]
    [Google Scholar]
  12. Gavazzi C., Yver M., Isel C., Smyth R. P., Rosa-Calatrava M., Lina B., Moulès V., Marquet R. 2013; A functional sequence-specific interaction between influenza A virus genomic RNA segments. Proc Natl Acad Sci U S A 110:16604–16609 [View Article][PubMed]
    [Google Scholar]
  13. González S. A., Mattion N. M., Bellinzoni R., Burrone O. R. 1989; Structure of rearranged genome segment 11 in two different rotavirus strains generated by a similar mechanism. J Gen Virol 70:1329–1336 [View Article][PubMed]
    [Google Scholar]
  14. Gorziglia M., Nishikawa K., Fukuhara N. 1989; Evidence of duplication and deletion in super short segment 11 of rabbit rotavirus Alabama strain. Virology 170:587–590 [View Article][PubMed]
    [Google Scholar]
  15. 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]
  16. 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]
  17. Hua J., Patton J. T. 1994; The carboxyl-half of the rotavirus nonstructural protein NS53 (NSP1) is not required for virus replication. Virology 198:567–576 [View Article][PubMed]
    [Google Scholar]
  18. Hundley F., Biryahwaho B., Gow M., Desselberger U. 1985; Genome rearrangements of bovine rotavirus after serial passage at high multiplicity of infection. Virology 143:88–103 [View Article][PubMed]
    [Google Scholar]
  19. Joklik W. editor 1983 The Reoviridae New York: Plenum Press; [CrossRef]
    [Google Scholar]
  20. Lawton J. A., Zeng C. Q., Mukherjee S. K., Cohen J., Estes M. K., Prasad B. V. 1997; Three-dimensional structural analysis of recombinant rotavirus-like particles with intact and amino-terminal-deleted VP2: implications for the architecture of the VP2 capsid layer. J Virol 71:7353–7360[PubMed]
    [Google Scholar]
  21. Lorenz R, Bernhart S. H., Höner Zu Siederdissen C., Tafer H., Flamm C., Stadler P. F., Hofacker I.L. 2011; ViennaRNA Package 2.0. Algorithms . Mol Biol 6:26 [View Article][PubMed]
    [Google Scholar]
  22. Martin S. A., Zweerink H. J. 1972; Isolation and characterization of two types of bluetongue virus particles. Virology 50:495–506 [View Article][PubMed]
    [Google Scholar]
  23. Matsui S. M., Mackow E. R., Matsuno S., Paul, P S., Greenberg H. B. 1990; Sequence analysis of gene 11 equivalents from “short” and “super short” strains of rotavirus. J Virol 64, 120–124
    [Google Scholar]
  24. Matsuo E., Roy P. 2009; Bluetongue virus VP6 acts early in the replication cycle and can form the basis of chimeric virus formation. J Virol 83:8842–8848 [View Article][PubMed]
    [Google Scholar]
  25. Mellor P. S., Hamblin C. 2004; African horse sickness. Vet Res 35:445–466 [View Article][PubMed]
    [Google Scholar]
  26. Méndez E., Arias C. F., López S. 1992; Genomic rearrangements in human rotavirus strain Wa; analysis of rearranged RNA segment 7. Arch Virol 125:331–338 [View Article][PubMed]
    [Google Scholar]
  27. Mindich L. 1999; Precise packaging of the three genomic segments of the double-stranded-RNA bacteriophage phi6. Microbiol Mol Biol Rev 63, 149–160
    [Google Scholar]
  28. Modrof J., Lymperopoulos K., Roy P. 2005; Phosphorylation of bluetongue virus nonstructural protein 2 is essential for formation of viral inclusion bodies. J Virol 79:10023–10031 [View Article][PubMed]
    [Google Scholar]
  29. Morgan E. M., Zweerink H. J. 1975; Characterization of transcriptase and replicase particles isolated from reovirus-infected cells. Virology 68:455–466 [View Article][PubMed]
    [Google Scholar]
  30. Nakagawa, A., Miyazaki, N., Taka, J., Naitow, H., Ogawa, A., Fujimoto, Z., Mizuno, H., Higashi, T., Watanabe, Y. & other authors 2003; The atomic structure of rice dwarf virus reveals the self-assembly mechanism of component proteins. Structure 11:1227–1238 [View Article][PubMed]
    [Google Scholar]
  31. Parashar U. D., Gibson C. J., Bresee J. S., Glass R. I. 2006; Rotavirus and severe childhood diarrhea. Emerg Infect Dis 12:304–306 [View Article][PubMed]
    [Google Scholar]
  32. Patel A., Roy P. 2014; The molecular biology of Bluetongue virus replication. Virus Res 182:5–20 [View Article][PubMed]
    [Google Scholar]
  33. Pedley S., Hundley F., Chrystie I., McCrae M. A., Desselberger U. 1984; The genomes of rotaviruses isolated from chronically infected immunodeficient children. J Gen Virol 65:1141–1150 [View Article][PubMed]
    [Google Scholar]
  34. Pesavento J. B., Crawford S. E., Estes M. K., Prasad B. V. 2006; Rotavirus proteins: structure and assembly. Curr Top Microbiol Immunol 309:189–219[PubMed]
    [Google Scholar]
  35. Qiao X., Casini G., Qiao J., Mindich L. 1995; In vitro packaging of individual genomic segments of bacteriophage phi 6 RNA: serial dependence relationships. J Virol 69, 2926–2931
    [Google Scholar]
  36. Reinisch K. M., Nibert M. L., Harrison S. C. 2000; Structure of the reovirus core at 3.6 Å resolution. Nature 404:960–967 [View Article][PubMed]
    [Google Scholar]
  37. Roner M. R., Joklik W. K. 2001; Reovirus reverse genetics: incorporation of the CAT gene into the reovirus genome. Proc Natl Acad Sci U S A 98:8036–8041 [View Article][PubMed]
    [Google Scholar]
  38. Roner M. R., Roehr J. 2006; The 3′ sequences required for incorporation of an engineered ssRNA into the Reovirus genome. Virol J 3:1 [View Article][PubMed]
    [Google Scholar]
  39. Roner M. R., Steele B. G. 2007a; Localizing the reovirus packaging signals using an engineered m1 and s2 ssRNA. Virology 358:89–97 [View Article][PubMed]
    [Google Scholar]
  40. Roner M. R., Steele B. G. 2007b; Features of the mammalian orthoreovirus 3 Dearing l1 single-stranded RNA that direct packaging and serotype restriction. J Gen Virol 88:3401–3412 [View Article][PubMed]
    [Google Scholar]
  41. Roner M. R., Bassett K., Roehr J. 2004; Identification of the 5′ sequences required for incorporation of an engineered ssRNA into the Reovirus genome. Virology 329:348–360 [View Article][PubMed]
    [Google Scholar]
  42. Sambrook J., Russell D. W. 2001 Molecular Cloning: A Laboratory Manual, 3rd edn Cold Spring Harbor, NY: Cold Spring Harbor Laboratory
    [Google Scholar]
  43. Scott G. E., Tarlow O., McCrae M. A. 1989; Detailed structural analysis of a genome rearrangement in bovine rotavirus. Virus Res 14:119–127 [View Article][PubMed]
    [Google Scholar]
  44. Sung P. Y., Roy P. 2014; Sequential packaging of RNA genomic segments during the assembly of Bluetongue virus. Nucleic Acids Res 42:13824–13838 [View Article][PubMed]
    [Google Scholar]
  45. Thompson J. D., Higgins D. G., Gibson T. J. 1994; clustal w: improving the sensitivity of progressive multiple sequence alignment through sequence weighting, position-specific gap penalties and weight matrix choice. Nucleic Acids Res 22:4673–4680 [View Article][PubMed]
    [Google Scholar]
  46. Tian Y., Tarlow O., Ballard A., Desselberger U., McCrae M. A. 1993; Genomic concatemerization/deletion in rotaviruses: a new mechanism for generating rapid genetic change of potential epidemiological importance. J Virol 67:6625–6632[PubMed]
    [Google Scholar]
  47. Troupin C., Schnuriger A., Duponchel S., Deback C., Schnepf N., Dehee A., Garbarg-Chenon A. 2011; Rotavirus rearranged genomic RNA segments are preferentially packaged into viruses despite not conferring selective growth advantage to viruses. PLoS One 6:e20080 [View Article][PubMed]
    [Google Scholar]
  48. Turner D. H., Mathews D. H. 2010; NNDB: the nearest neighbor parameter database for predicting stability of nucleic acid secondary structure. Nucleic Acids Res 38:D280–D282 [View Article][PubMed]
    [Google Scholar]
  49. Valdar W. S. 2002; Scoring residue conservation. Proteins 48:227–241 [View Article][PubMed]
    [Google Scholar]
  50. Verwoerd D. W., Huismans H. 1972; Studies on the in vitro and the in vivo transcription of the bluetongue virus genome. Onderstepoort J Vet Res 39:185–191[PubMed]
    [Google Scholar]
  51. Verwoerd D. W., Els H. J., De Villiers E. M., Huismans H. 1972; Structure of the bluetongue virus capsid. J Virol 10:783–794[PubMed]
    [Google Scholar]
  52. Zuker M. 2003; Mfold web server for nucleic acid folding and hybridization prediction. Nucleic Acids Res 31:3406–3415 [View Article][PubMed]
    [Google Scholar]
  53. Zweerink H. J. 1974; Multiple forms of SS → DS RNA polymerase activity in reovirus-infected cells. Nature 247:313–315 [View Article][PubMed]
    [Google Scholar]
  54. Zweerink H. J., Ito Y., Matsuhisa T. 1972; Synthesis of reovirus double-stranded RNA within virionlike particles. Virology 50:349–358 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.000400
Loading
/content/journal/jgv/10.1099/jgv.0.000400
Loading

Data & Media loading...

Supplements

Supplementary Data

PDF
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