1887

Abstract

The 2A protein appears to be diverse among picornaviruses, in contrast to the other non-structural proteins, which have homologous structures and functions. In enteroviruses and rhinoviruses, 2A is a trypsin-like protease involved in protein processing and in shut-off of host-cell macromolecular synthesis. The aphthovirus and cardiovirus 2A is associated with an unusual processing event at the 2A/2B junction. It is shown here that the 2A protein of several diverse picornaviruses, the human parechoviruses, Aichi virus and avian encephalomyelitis virus, possess previously unrecognized conserved motifs and are likely to have a common function. Moreover, these motifs, a conserved histidine and flanking amino acids, an asparagine–cysteine dipeptide and a putative transmembrane domain, are characteristic of a family of cellular proteins, at least two of which are involved in the control of cell growth. These observations have important implications for an understanding of picornavirus genome structure and evolution, as well as pointing to possible functions of 2A in these viruses.

Loading

Article metrics loading...

/content/journal/jgv/10.1099/0022-1317-81-1-201
2000-01-01
2024-05-06
Loading full text...

Full text loading...

/deliver/fulltext/jgv/81/1/0810201a.html?itemId=/content/journal/jgv/10.1099/0022-1317-81-1-201&mimeType=html&fmt=ahah

References

  1. Altschul, S. F., Gish, W., Miller, W., Myers, E. W. & Lipman, D. J. (1990). Basic local alignment search tool. Journal of Molecular Biology 215, 403-410.[CrossRef] [Google Scholar]
  2. Chang, K. H., Auvinen, P., Hyypiä, T. & Stanway, G. (1989). The nucleotide sequence of coxsackievirus A9: implications for receptor binding and enterovirus classification. Journal of General Virology 70, 3269-3280.[CrossRef] [Google Scholar]
  3. Chang, K. H., Day, C., Walker, J., Hyypiä, T. & Stanway, G. (1992). The nucleotide sequences of wild-type coxsackievirus A9 strains imply that an RGD motif in VP1 is functionally significant. Journal of General Virology 73, 621-626.[CrossRef] [Google Scholar]
  4. Dingle, K. E., Lambden, P. R., Caul, E. O. & Clarke, I. N. (1995). Human enteric Caliciviridae: the complete genome sequence and expression of virus-like particles from a genetic group II small round structured virus. Journal of General Virology 76, 2349-2355.[CrossRef] [Google Scholar]
  5. DiSepio, D., Ghosn, C., Eckert, R. L., Deucher, A., Robinson, N., Duvic, M., Chandraratna, R. A. S. & Nagpal, S. (1998). Identification and characterization of a retinoid-induced class II tumor suppressor/growth regulatory gene. Proceedings of the National Academy of Sciences, USA 95, 14811-14815.[CrossRef] [Google Scholar]
  6. Doherty, M., Todd, D., McFerran, N. & Hoey, E. M. (1999). Sequence analysis of a porcine enterovirus serotype 1 isolate: relationships with other picornaviruses. Journal of General Virology 80, 1929-1941. [Google Scholar]
  7. Ghazi, F., Hughes, P. J., Hyypiä, T. & Stanway, G. (1998). Molecular analysis of human parechovirus type 2 (formerly echovirus 23). Journal of General Virology 79, 2641-2650. [Google Scholar]
  8. Gorbalenya, A. E. (1992). Host-related sequences in RNA viral genomes. Seminars in Virology 3, 359-371. [Google Scholar]
  9. Hajnal, A., Klemenz, R. & Schafer, R. (1994). Subtraction cloning of H-rev107, a gene specifically expressed in H-ras resistant fibroblasts. Oncogene 9, 479-490. [Google Scholar]
  10. Hardy, M. E. & Estes, M. K. (1996). Completion of the Norwalk virus genome sequence. Virus Genes 12, 287-290. [Google Scholar]
  11. Hofmann, K. & Stoffel, W. (1993). TMbase – a database of membrane spanning protein segments. Biological Chemistry Hoppe-Seyler 374, 166. [Google Scholar]
  12. Hughes, P. J., Horsnell, C., Hyypiä, T. & Stanway, G. (1995). The coxsackievirus A9 RGD motif is not essential for virus viability. Journal of Virology 69, 8035-8040. [Google Scholar]
  13. Husmann, K., Sers, C., Fietze, E., Mincheva, A., Lichter, P. & Schafer, R. (1998). Transcriptional and translational downregulation of H-REV107, a class II tumour suppressor gene located on human chromosome 11q11-12. Oncogene 17, 1305-1312.[CrossRef] [Google Scholar]
  14. Hyypiä, T., Horsnell, C., Maaronen, M., Khan, M., Kalkkinen, N., Auvinen, P., Kinnunen, L. & Stanway, G. (1992). A distinct picornavirus group identified by sequence analysis. Proceedings of the National Academy of Sciences, USA 89, 8847-8851.[CrossRef] [Google Scholar]
  15. Jamison, R. M. (1974). An electron microscopic study of the intracellular development of echovirus 22.Archiv für die gesamte Virusforschung 44, 184-194.[CrossRef] [Google Scholar]
  16. Jia, X. Y., Summers, D. F. & Ehrenfeld, E. (1993). Primary cleavage of the HAV capsid protein precursor in the middle of the proposed 2A coding region. Virology 193, 515-519.[CrossRef] [Google Scholar]
  17. King, A. M. Q., Brown, F., Christian, P., Hovi, T., Hyypiä, T., Knowles, N. J., Lemon, S. M., Minor, P. D., Palmenberg, A. C., Skern, T. & Stanway, G. (1999). Picornaviridae. In Virus Taxonomy. Seventh Report of the International Committee on Taxonomy of Viruses. Edited by M. H. V. Van Regenmortel, C. M. Fauquet, D. H. L. Bishop, C. H. Calisher, E. B. Carsten, M. K. Estes, S. M. Lemon, J. Maniloff, M. A. Mayo, D. J. McGeoch, C. R. Pringle & R. B. Wickner. New York & San Diego: Academic Press (in press).
  18. Lambden, P. R., Caul, E. O., Ashley, C. R. & Clarke, I. N. (1993). Sequence and genome organization of a human small round-structured (Norwalk-like) virus. Science 259, 516-519.[CrossRef] [Google Scholar]
  19. Marvil, P., Knowles, N. J., Mockett, A. P. A., Britton, P., Brown, T. D. K. & Cavanagh, D. (1999). Avian encephalomyelitis virus is a picornavirus and is most closely related to hepatitis A virus. Journal of General Virology 80, 653-662. [Google Scholar]
  20. Niklasson, B., Hörnfeldt, B. & Lundman, B. (1998). Could myocarditis, insulin-dependent diabetes mellitus, and Guillain–Barré syndrome be caused by one or more infectious agents carried by rodents? Emerging Infectious Diseases 4, 187-193.[CrossRef] [Google Scholar]
  21. Niklasson, B., Kinnunen, L., Hörnfeldt, B., Hörling, J., Benemar, C., Hedlund, K. O., Matskova, L., Hyypiä, T. & Winberg, G. (1999). A new picornavirus isolated from bank voles (Clethrionomys glareolus). Virology 255, 86-93.[CrossRef] [Google Scholar]
  22. Oberste, M. S., Maher, K. & Pallansch, M. A. (1998). Complete sequence of echovirus 23 and its relationship to echovirus 22 and other human enteroviruses. Virus Research 56, 217-223.[CrossRef] [Google Scholar]
  23. Pearson, W. R. & Lipman, D. J. (1988). Improved tools for biological sequence comparison. Proceedings of the National Academy of Sciences, USA 85, 2444-2448.[CrossRef] [Google Scholar]
  24. Rueckert, R. R. (1996).Picornaviridae: the viruses and their replication. In Fields Virology, pp. 609-654. Edited by B. N. Fields, D. M. Knipe & P. M. Howley. Philadelphia: Lippincott–Raven.
  25. Ruiz, A., Winston, A., Lim, Y.-H., Gilbert, B. A., Rando, R. R. & Bok, D. (1999). Molecular and biochemical characterization of lecithin retinol acyltransferase. Journal of Biological Chemistry 274, 3834-3841.[CrossRef] [Google Scholar]
  26. Ryan, M. D. & Flint, M. (1997). Virus-encoded proteinases of the picornavirus super-group. Journal of General Virology 78, 699-723. [Google Scholar]
  27. Ryan, M. D., Monaghan, S. & Flint, M. (1998). Virus-encoded proteinases of the Flaviviridae. Journal of General Virology 79, 947-959. [Google Scholar]
  28. Schultheiss, T., Emerson, S. U., Purcell, R. H. & Gauss-Muller, V. (1995). Polyprotein processing in echovirus 22: a first assessment.Biochemical and Biophysical Research Communications 217, 1120-1127.[CrossRef] [Google Scholar]
  29. Sers, C., Emmenegger, U., Husmann, K., Bucher, K., Andres, A. C. & Schafer, R. (1997). Growth-inhibitory activity and downregulation of the class II tumor-suppressor gene H-rev107 in tumor cell lines and experimental tumors. Journal of Cell Biology 136, 935-944.[CrossRef] [Google Scholar]
  30. Shaver, D. N., Barron, A. L. & Karzon, D. T. (1961). Distinctive cytopathology of ECHO viruses types 22 and 23. Proceedings of the Society for Experimental Biology and Medicine 106, 648-652.[CrossRef] [Google Scholar]
  31. Stanway, G. (1990). Structure, function and evolution of picornaviruses.Journal of General Virology 71, 2483-2501.[CrossRef] [Google Scholar]
  32. Stanway, G. & Hyypiä, T. (1999). Parechoviruses. Journal of Virology 73, 5249-5254. [Google Scholar]
  33. Stanway, G., Kalkkinen, N., Roivainen, M., Ghazi, F., Khan, M., Smyth, M., Meurman, O. & Hyypiä, T. (1994). Molecular and biological characteristics of echovirus 22, a representative of a new picornavirus group.Journal of Virology 68, 8232-8238. [Google Scholar]
  34. 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 Research 22, 4673-4680.[CrossRef] [Google Scholar]
  35. Wigand, R. & Sabin, A. B. (1961). Properties of ECHO types 22, 23 and 24 viruses. Archiv für die gesamte Virusforschung 11, 224-247.[CrossRef] [Google Scholar]
  36. Wutz, G., Auer, H., Nowotny, N., Grosse, B., Skern, T. & Kuechler, E. (1996). Equine rhinovirus serotypes 1 and 2: relationship to each other and to aphthoviruses and cardioviruses. Journal of General Virology 77, 1719-1730.[CrossRef] [Google Scholar]
  37. Yamashita, T., Sakae, K., Tsuzuki, H., Suzuki, Y., Ishikawa, N., Takeda, N., Miyamura, T. & Yamazaki, S. (1998). Complete nucleotide sequence and genetic organization of Aichi virus, a distinct member of the Picornaviridae associated with acute gastroenteritis in humans.Journal of Virology 72, 8408-8412. [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/0022-1317-81-1-201
Loading
/content/journal/jgv/10.1099/0022-1317-81-1-201
Loading

Data & Media loading...

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