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. 1988 Nov;62(11):4407–4409. doi: 10.1128/jvi.62.11.4407-4409.1988

Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex.

M A Devaney 1, V N Vakharia 1, R E Lloyd 1, E Ehrenfeld 1, M J Grubman 1
PMCID: PMC253884  PMID: 2845152

Abstract

Suppression of host protein synthesis in cells infected by poliovirus and certain other picornaviruses involves inactivation of the cap-binding protein complex. Inactivation of this complex has been correlated with the proteolytic cleavage of p220, a component of the cap-binding protein complex. Since picornaviral RNA is not capped, it continues to be translated as the cap-binding protein complex is inactivated. The cleavage of p220 can be induced to occur in vitro, catalyzed by extracts from infected cells or by reticulocyte lysates translating viral RNA. Expression of polioviral protease 2A is sufficient to induce p220 cleavage, and the presence in 2A of an 18-amino-acid sequence representing a putative cysteine protease active site correlates with the ability of different picornaviruses to induce p220 cleavage. Foot-and-mouth disease virus (FMDV) infection induces complete cleavage of p220, yet the FMDV genome codes for a 2A protein of only 16 amino acids, which does not include the putative cysteine protease active site. Using cDNA plasmids encoding various regions of the FMDV genome, we have determined that the leader protein is required to initiate p220 cleavage. This is the first report of a function for the leader protein, other than that of autocatalytic cleavage from the FMDV polyprotein.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bernstein H. D., Sonenberg N., Baltimore D. Poliovirus mutant that does not selectively inhibit host cell protein synthesis. Mol Cell Biol. 1985 Nov;5(11):2913–2923. doi: 10.1128/mcb.5.11.2913. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bonneau A. M., Sonenberg N. Proteolysis of the p220 component of the cap-binding protein complex is not sufficient for complete inhibition of host cell protein synthesis after poliovirus infection. J Virol. 1987 Apr;61(4):986–991. doi: 10.1128/jvi.61.4.986-991.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Burnette W. N. "Western blotting": electrophoretic transfer of proteins from sodium dodecyl sulfate--polyacrylamide gels to unmodified nitrocellulose and radiographic detection with antibody and radioiodinated protein A. Anal Biochem. 1981 Apr;112(2):195–203. doi: 10.1016/0003-2697(81)90281-5. [DOI] [PubMed] [Google Scholar]
  4. Etchison D., Fout S. Human rhinovirus 14 infection of HeLa cells results in the proteolytic cleavage of the p220 cap-binding complex subunit and inactivates globin mRNA translation in vitro. J Virol. 1985 May;54(2):634–638. doi: 10.1128/jvi.54.2.634-638.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Etchison D., Milburn S. C., Edery I., Sonenberg N., Hershey J. W. Inhibition of HeLa cell protein synthesis following poliovirus infection correlates with the proteolysis of a 220,000-dalton polypeptide associated with eucaryotic initiation factor 3 and a cap binding protein complex. J Biol Chem. 1982 Dec 25;257(24):14806–14810. [PubMed] [Google Scholar]
  6. Grubman M. J., Zellner M., Wagner J. Antigenic comparison of the polypeptides of foot-and-mouth disease virus serotypes and other picornaviruses. Virology. 1987 May;158(1):133–140. doi: 10.1016/0042-6822(87)90246-7. [DOI] [PubMed] [Google Scholar]
  7. Jen G., Detjen B. M., Thach R. E. Shutoff of HeLa cell protein synthesis by encephalomyocarditis virus and poliovirus: a comparative study. J Virol. 1980 Jul;35(1):150–156. doi: 10.1128/jvi.35.1.150-156.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kräusslich H. G., Nicklin M. J., Toyoda H., Etchison D., Wimmer E. Poliovirus proteinase 2A induces cleavage of eucaryotic initiation factor 4F polypeptide p220. J Virol. 1987 Sep;61(9):2711–2718. doi: 10.1128/jvi.61.9.2711-2718.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Laemmli U. K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970 Aug 15;227(5259):680–685. doi: 10.1038/227680a0. [DOI] [PubMed] [Google Scholar]
  10. Lloyd R. E., Etchison D., Ehrenfeld E. Poliovirus protease does not mediate cleavage of the 220,000-Da component of the cap binding protein complex. Proc Natl Acad Sci U S A. 1985 May;82(9):2723–2727. doi: 10.1073/pnas.82.9.2723. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lloyd R. E., Grubman M. J., Ehrenfeld E. Relationship of p220 cleavage during picornavirus infection to 2A proteinase sequencing. J Virol. 1988 Nov;62(11):4216–4223. doi: 10.1128/jvi.62.11.4216-4223.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Lloyd R. E., Jense H. G., Ehrenfeld E. Restriction of translation of capped mRNA in vitro as a model for poliovirus-induced inhibition of host cell protein synthesis: relationship to p220 cleavage. J Virol. 1987 Aug;61(8):2480–2488. doi: 10.1128/jvi.61.8.2480-2488.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Lloyd R. E., Toyoda H., Etchison D., Wimmer E., Ehrenfeld E. Cleavage of the cap binding protein complex polypeptide p220 is not effected by the second poliovirus protease 2A. Virology. 1986 Apr 15;150(1):299–303. doi: 10.1016/0042-6822(86)90291-6. [DOI] [PubMed] [Google Scholar]
  14. Robertson B. H., Grubman M. J., Weddell G. N., Moore D. M., Welsh J. D., Fischer T., Dowbenko D. J., Yansura D. G., Small B., Kleid D. G. Nucleotide and amino acid sequence coding for polypeptides of foot-and-mouth disease virus type A12. J Virol. 1985 Jun;54(3):651–660. doi: 10.1128/jvi.54.3.651-660.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Rueckert R. R., Wimmer E. Systematic nomenclature of picornavirus proteins. J Virol. 1984 Jun;50(3):957–959. doi: 10.1128/jvi.50.3.957-959.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Shatkin A. J. mRNA cap binding proteins: essential factors for initiating translation. Cell. 1985 Feb;40(2):223–224. doi: 10.1016/0092-8674(85)90132-1. [DOI] [PubMed] [Google Scholar]
  17. Strebel K., Beck E. A second protease of foot-and-mouth disease virus. J Virol. 1986 Jun;58(3):893–899. doi: 10.1128/jvi.58.3.893-899.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Summers D. F., Maizel J. V., Jr, Darnell J. E., Jr Evidence for virus-specific noncapsid proteins in poliovirus-infected HeLa cells. Proc Natl Acad Sci U S A. 1965 Aug;54(2):505–513. doi: 10.1073/pnas.54.2.505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Tahara S. M., Morgan M. A., Shatkin A. J. Two forms of purified m7G-cap binding protein with different effects on capped mRNA translation in extracts of uninfected and poliovirus-infected HeLa cells. J Biol Chem. 1981 Aug 10;256(15):7691–7694. [PubMed] [Google Scholar]
  20. Vakharia V. N., Devaney M. A., Moore D. M., Dunn J. J., Grubman M. J. Proteolytic processing of foot-and-mouth disease virus polyproteins expressed in a cell-free system from clone-derived transcripts. J Virol. 1987 Oct;61(10):3199–3207. doi: 10.1128/jvi.61.10.3199-3207.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]

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