1887

Abstract

2A is an oligopeptide sequence mediating a ribosome ‘skipping’ effect, producing an apparent ‘cleavage’ of polyproteins. First identified and characterized in picornaviruses, ‘2A-like’ sequences are found in other mammalian viruses and a wide range of insect viruses. Databases were analysed using a motif conserved amongst 2A/2A-like sequences. The newly identified 2A-like sequences (30 aa) were inserted into a reporter polyprotein to determine their cleavage activity. Our analyses showed that these sequences fall into two categories. The majority mediated very high (complete) cleavage to separate proteins and a few sequences mediated cleavage with lower efficiency, generating appreciable levels of the uncleaved form. Phylogenetic analyses of 2A-like sequences and RNA-dependent RNA polymerases (RdRps) indicated multiple, independent, acquisitions of these sequences at different stages during virus evolution. Within a virus family, 2A sequences are (probably) homologous, but diverge due to other evolutionary pressures. Amongst different families, however, 2A/2A-like sequences appear to be homoplasic.

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2008-04-01
2024-12-13
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References

  1. Carrillo C., Tulman E. R., Delhon G., Lu Z., Carreno A., Vagnozzi A., Kutish G. F., Rock D. L. 2005; Comparative genomics of foot-and-mouth disease virus. J Virol 79:6487–6504 [CrossRef]
    [Google Scholar]
  2. de Felipe P., Hughes L. E., Ryan M. D., Brown J. D. 2003; Co-translational, intra-ribosomal cleavage of foot-and-mouth disease virus 2A peptide. J Biol Chem 278:11441–11448 [CrossRef]
    [Google Scholar]
  3. de Miranda J. R., Drebot M., Tyler S., Shen M., Cameron C. E., Stoltz D. B., Camazine S. M. 2004; Complete nucleotide sequence of Kashmir bee virus and comparison with acute bee paralysis virus. J Gen Virol 85:2263–2270 [CrossRef]
    [Google Scholar]
  4. Donnelly M. L. L., Gani D., Flint M., Monoghan S., Ryan M. D. 1997; The cleavage activity of aphth- and cardiovirus 2A proteins. J Gen Virol 78:13–21
    [Google Scholar]
  5. Donnelly M. L. L., Luke G., Mehrotra A., Li X., Hughes L. E., Gani D., Ryan M. D. 2001a; Analysis of aphthovirus 2A/2B polyprotein ‘cleavage’ mechanism indicates not a proteolytic reaction, but a novel translational effect: a putative ribosomal ‘skip’. J Gen Virol 82:1013–1025
    [Google Scholar]
  6. Donnelly M. L. L., Hughes L. E., Luke G., Mendoza H., Ten Dam E., Gani D., Ryan M. D. 2001b; The ‘cleavage’ activities of foot-and-mouth disease virus 2A site-directed mutants and naturally occurring ‘2A-like’ sequences. J Gen Virol 82:1027–1041
    [Google Scholar]
  7. Fujiyuki T., Takeuchi H., Ono M., Ohka S., Sasaki T., Nomoto A., Kubo T. 2004; Novel insect picorna-like virus identified in the brains of aggressive worker honeybees. J Virol 78:1093–1100 [CrossRef]
    [Google Scholar]
  8. Gorbalenya A. E., Pringle F. M., Zeddam J. L., Luke B. T., Cameron C. E., Kalmakoff J., Hanzlik T. N., Gordon K. H. J., Ward V. K. 2002; The palm subdomain-based active site is internally permuted in viral RNA-dependent RNA polymerases of an ancient lineage. J Mol Biol 324:47–62 [CrossRef]
    [Google Scholar]
  9. Govan V. A., Leat N., Allsopp M., Davison S. 2000; Analysis of the complete genome sequence of acute bee paralysis virus shows that it belongs to the novel group of insect-infecting RNA viruses. Virology 277:457–463 [CrossRef]
    [Google Scholar]
  10. Graham R. I., Rao S., Possee R. D., Sait S. M., Mertens P. P. C., Hails R. S. 2006; Detection and characterization of three novel species of reovirus ( Reoviridae ), isolated from geographically separate populations of the winter moth Operophtera brumata (Lepidoptera: Geometridae) on Orkney. J Invertebr Pathol 91:79–87 [CrossRef]
    [Google Scholar]
  11. Hagiwara K., Kobayashi J., Tomita M., Yoshimura T. 2001; Nucleotide sequence of genome segment 5 from Bombyx mori cypovirus 1. Arch Virol 146:181–187 [CrossRef]
    [Google Scholar]
  12. Heath L., van der Walt E., Varsani A., Martin D. P. 2006; Recombination patterns in aphthoviruses mirror those found in other picornaviruses. J Virol 80:11827–11832 [CrossRef]
    [Google Scholar]
  13. Hughes L. 2003; Analysis of the Foot-and-mouth disease virus 2A-mediated polyprotein processing event . PhD thesis University of St Andrews;
  14. Isawa H., Asano S., Sahara K., Iizuka T., Bando H. 1998; Analysis of genetic information of an insect picorna-like virus, infectious flacherie virus of silkworm: evidence for evolutionary relationships among insects, mammalian and plant picorna(-like) viruses. Arch Virol 143:127–143 [CrossRef]
    [Google Scholar]
  15. Jayaram H., Estes M. K., Prasad B. V. 2004; Emerging themes in rotavirus cell entry, genome organization, transcription and replication. Virus Res 101:67–81 [CrossRef]
    [Google Scholar]
  16. Jones M. S., Lukashov V. V., Ganac R. D., Schnurr D. P. 2007; Discovery of a novel human picornavirus in a stool sample from a pediatric patient presenting with fever of unknown origin. J Clin Microbiol 45:2144–2150 [CrossRef]
    [Google Scholar]
  17. Kim M. C., Kwon Y. K., Joh S. J., Lindberg A. M., Kwon J. H., Kim J. H., Kim S. J. 2006; Molecular analysis of duck hepatitis virus type 1 reveals a novel lineage close to the genus Parechovirus in the family Picornaviridae . J Gen Virol 87:3307–3316 [CrossRef]
    [Google Scholar]
  18. Langland J. O., Pettiford S., Jiang B., Jacobs B. L. 1994; Products of the porcine group C rotavirus NSP3 gene bind specifically to double-stranded RNA and inhibit activation of the interferon-induced protein kinase PKR. J Virol 68:3821–3829
    [Google Scholar]
  19. Lanzi G., de Miranda J. R., Boniotti M. B., Cameron C. E., Lavazza A., Capucci L., Camazine S. M., Rossi C. 2006; Molecular and biological characterization of deformed wing virus of honeybees ( Apis mellifera L.). J Virol 80:4998–5009 [CrossRef]
    [Google Scholar]
  20. Lindberg A. M., Johansson S. 2002; Phylogenetic analysis of Ljungan virus and A-2 plaque virus, new members of the Picornaviridae . Virus Res 85:61–70 [CrossRef]
    [Google Scholar]
  21. Lukashev A. N. 2005; Role of recombination in evolution of enteroviruses. Rev Med Virol 15:157–167 [CrossRef]
    [Google Scholar]
  22. Maori E., Tanne E., Sela I. 2007; Reciprocal sequence exchange between non-retro viruses and hosts leading to the appearance of new host phenotypes. Virology 362:342–349 [CrossRef]
    [Google Scholar]
  23. Nibert M. L. 2007; ‘2A-like’ and ‘shifty heptamer’ motifs in penaeid shrimp infectious myonecrosis virus, a monosegmented double-stranded RNA virus. J Gen Virol 88:1315–1318 [CrossRef]
    [Google Scholar]
  24. Oem J. K., Lee K. N., Cho I. S., Kye S. J., Park J. H., Joo Y. S. 2004; Comparison and analysis of the complete nucleotide sequence of foot-and-mouth disease viruses from animals in Korea and other PanAsia strains. Virus Genes 29:63–71 [CrossRef]
    [Google Scholar]
  25. Ohsawa K., Watanabe Y., Miyata H., Sato H. 2003; Genetic analysis of a Theiler-like virus isolated from rats. Comp Med 53:191–196
    [Google Scholar]
  26. Ongus J. R., Peters D., Bonmatin J.-M., Bengsch E., Vlak J. M., van Oers M. M. 2004; Complete sequence of a picorna-like virus of the genus Iflavirus replicating in the mite Varroa destructor . J Gen Virol 85:3747–3755 [CrossRef]
    [Google Scholar]
  27. Piron M., Delaunay T., Grosclaude J., Poncet D. 1999; Identification of the RNA-binding, dimerization, and eIF4GI-binding domains of rotavirus nonstructural protein NSP3. J Virol 73:5411–5421
    [Google Scholar]
  28. Poulos B. T., Tang K. F., Pantoja C. R., Bonami J. R., Lightner D. V. 2006; Purification and characterization of infectious myonecrosis virus of penaeid shrimp. J Gen Virol 87:987–996 [CrossRef]
    [Google Scholar]
  29. Pringle F. M., Johnson K. N., Goodman C. L., McIntosh A. H., Ball L. A. 2003; Providence virus: a new member of the Tetraviridae that infects cultured insect cells. Virology 306:359–370 [CrossRef]
    [Google Scholar]
  30. Rao S., Carner G. R., Scott S. W., Omura T., Hagiwara K. 2003; Comparison of the amino acid sequences of RNA-dependent RNA polymerases of cypoviruses in the family Reoviridae . Arch Virol 148:209–219 [CrossRef]
    [Google Scholar]
  31. Ryan M. D., Drew J. 1994; Foot-and-mouth disease virus 2A oligopeptide mediated cleavage of an artificial polyprotein. EMBO J 13:928–933
    [Google Scholar]
  32. Ryan M. D., Donnelly M. L. L., Lewis A., Mehrotra A. P., Wilkie J., Gani D. 1999; A model for non-stoichiometric, co-translational protein scission in eukaryotic ribosomes. Bioorg Chem 27:55–79 [CrossRef]
    [Google Scholar]
  33. 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 [CrossRef]
    [Google Scholar]
  34. Thompson J. D., Gibson T. J., Plewniak F., Jeanmougin F., Higgins D. G. 1997; The clustal_x windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882 [CrossRef]
    [Google Scholar]
  35. Tseng C. H., Tsai H. J. 2007; Molecular characterization of a new serotype of duck hepatitis virus. Virus Res 126:19–31 [CrossRef]
    [Google Scholar]
  36. Tseng C. H., Knowles N. J., Tsai H. J. 2007; Molecular analysis of duck hepatitis virus type 1 indicates that it should be assigned to a new genus. Virus Res 123:190–203 [CrossRef]
    [Google Scholar]
  37. Valles S. M., Strong C. A., Dang P. M., Hunter W. B., Pereira R. M., Oi D. H., Shapiro A. M., Williams D. F. 2004; A picorna-like virus from the red imported fire ant, Solenopsis invicta : initial discovery, genome sequence, and characterization. Virology 328:151–157 [CrossRef]
    [Google Scholar]
  38. van der Wilk F., Dullemans A. M., Verbeek M., van den Heuvel J. F. J. M. 1997; Nucleotide sequence and genomic organization of Acyrthosiphon pisum virus. Virology 238:353–362 [CrossRef]
    [Google Scholar]
  39. Wang X., Yhang J., Lu J., Yi F., Liu C., Hu Y. 2004; Sequence analysis and genomic organization of a new insect picorna-like virus, Ectropis obliqua picorna-like virus, isolated from Ectropis obliqua . J Gen Virol 85:1145–1151 [CrossRef]
    [Google Scholar]
  40. Wu C. Y., Lo C. F., Huang C. J., Yu H. T., Wang C. H. 2002; The complete genome sequence of Perina nuda picorna-like virus, an insect-infecting RNA virus with a genome organization similar to that of the mammalian picornaviruses. Virology 294:312–323 [CrossRef]
    [Google Scholar]
  41. Yang H., Makeyev E. V., Kang Z., Ji S., Bamford D. H., van Dijk A. A. 2004; Cloning and sequence analysis of dsRNA segments 5, 6 and 7 of a novel non-group A, B, C adult rotavirus that caused an outbreak of gastroenteritis in China. Virus Res 106:15–26 [CrossRef]
    [Google Scholar]
  42. Zell R., Dauber M., Krumbholz A., Henke A., Birch-Hirschfeld E., Stelzner A., Prager D., Wurm R. 2001; Porcine teschoviruses comprise at least eleven distinct serotypes: molecular and evolutionary aspects. J Virol 75:1620–1631 [CrossRef]
    [Google Scholar]
  43. Zhao S. L., Liang C. Y., Hong J. J., Peng H. Y. 2003; Genomic sequence analysis of segments 1 to 6 of Dendrolimus punctatus cytoplasmic polyhedrosis virus. Arch Virol 148:1357–1368
    [Google Scholar]
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