Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1987 Apr;61(4):986–991. doi: 10.1128/jvi.61.4.986-991.1987

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.

A M Bonneau, N Sonenberg
PMCID: PMC254054  PMID: 3029432

Abstract

Infection of cells with poliovirus results in the complete shutoff of host protein synthesis. It is presumed that proteolysis of the p220 component of the cap-binding protein complex that is required for the translation of host mRNAs is responsible for the shutoff phenomenon. In this paper, we show that when cells are infected with poliovirus in the presence of guanidine or 3-methylquercetin, both inhibitors of poliovirus replication, complete cleavage of p220 occurs by 3.5 h postinfection. However, under these conditions only 55 to 77% of host protein synthesis is suppressed. Results obtained with extracts prepared from poliovirus-infected cells were similar to those obtained in vivo. These results suggest that complete inhibition of host protein synthesis after poliovirus infection requires at least one event in addition to proteolysis of p220. Thus, proteolysis of p220 is probably necessary but not sufficient for total suppression of host protein synthesis after poliovirus infection.

Full text

PDF
986

Images in this article

987Image
on p.987
988Image
on p.988
988Image
on p.988
989Image
on p.989
989Image
on p.989

Selected References

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

  1. Asselbergs F. A., Peters W. H., van Venrooij W. J., Bloemendal H. Cap analogues do not inhibit mRNA translation in Xenopus laevis oocytes. FEBS Lett. 1978 Oct 15;94(2):195–198. doi: 10.1016/0014-5793(78)80936-3. [DOI] [PubMed] [Google Scholar]
  2. BABLANIAN R., EGGERS H. J., TAMM I. STUDIES ON THE MECHANISM OF POLIOVIRUS-INDUCED CELL DAMAGE. I. THE RELATION BETWEEN POLIOVIRUS,-INDUCED METABOLIC AND MORPHOLOGICAL ALTERATIONS IN CULTURED CELLS. Virology. 1965 May;26:100–113. doi: 10.1016/0042-6822(65)90030-9. [DOI] [PubMed] [Google Scholar]
  3. Bablanian R. Depression of macromolecular synthesis in cells infected with guanidine-dependent poliovirus under restrictive conditions. Virology. 1972 Jan;47(1):255–259. doi: 10.1016/0042-6822(72)90260-7. [DOI] [PubMed] [Google Scholar]
  4. Banerjee A. K. 5'-terminal cap structure in eucaryotic messenger ribonucleic acids. Microbiol Rev. 1980 Jun;44(2):175–205. doi: 10.1128/mr.44.2.175-205.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Bonneau A. M., Darveau A., Sonenberg N. Effect of viral infection on host protein synthesis and mRNA association with the cytoplasmic cytoskeletal structure. J Cell Biol. 1985 Apr;100(4):1209–1218. doi: 10.1083/jcb.100.4.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Borgert K., Koschel K., Täuber H., Wecker E. Effect of inactivation by hydroxylamine on early functions of poliovirus. J Virol. 1971 Jul;8(1):1–6. doi: 10.1128/jvi.8.1.1-6.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Carrasco L., Smith A. E. Sodium ions and the shut-off of host cell protein synthesis by picornaviruses. Nature. 1976 Dec 23;264(5588):807–809. doi: 10.1038/264807a0. [DOI] [PubMed] [Google Scholar]
  9. Castrillo J. L., Vanden Berghe D., Carrasco L. 3-Methylquercetin is a potent and selective inhibitor of poliovirus RNA synthesis. Virology. 1986 Jul 15;152(1):219–227. doi: 10.1016/0042-6822(86)90386-7. [DOI] [PubMed] [Google Scholar]
  10. Drummond D. R., Armstrong J., Colman A. The effect of capping and polyadenylation on the stability, movement and translation of synthetic messenger RNAs in Xenopus oocytes. Nucleic Acids Res. 1985 Oct 25;13(20):7375–7394. doi: 10.1093/nar/13.20.7375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Edery I., Hümbelin M., Darveau A., Lee K. A., Milburn S., Hershey J. W., Trachsel H., Sonenberg N. Involvement of eukaryotic initiation factor 4A in the cap recognition process. J Biol Chem. 1983 Sep 25;258(18):11398–11403. [PubMed] [Google Scholar]
  12. Edery I., Lee K. A., Sonenberg N. Functional characterization of eukaryotic mRNA cap binding protein complex: effects on translation of capped and naturally uncapped RNAs. Biochemistry. 1984 May 22;23(11):2456–2462. doi: 10.1021/bi00306a021. [DOI] [PubMed] [Google Scholar]
  13. Etchison D., Hansen J., Ehrenfeld E., Edery I., Sonenberg N., Milburn S., Hershey J. W. Demonstration in vitro that eucaryotic initiation factor 3 is active but that a cap-binding protein complex is inactive in poliovirus-infected HeLa cells. J Virol. 1984 Sep;51(3):832–837. doi: 10.1128/jvi.51.3.832-837.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  16. Fernandez-Munoz R., Darnell J. E. Structural difference between the 5' termini of viral and cellular mRNA in poliovirus-infected cells: possible basis for the inhibition of host protein synthesis. J Virol. 1976 May;18(2):719–726. doi: 10.1128/jvi.18.2.719-726.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Grifo J. A., Tahara S. M., Morgan M. A., Shatkin A. J., Merrick W. C. New initiation factor activity required for globin mRNA translation. J Biol Chem. 1983 May 10;258(9):5804–5810. [PubMed] [Google Scholar]
  18. HOLLAND J. J. INHIBITION OF HOST CELL MACROMOLECULAR SYNTHESIS BY HIGH MULTIPLICITIES OF POLIOVIRUS UNDER CONDITIONS PREVENTING VIRUS SYNTHESIS. J Mol Biol. 1964 Apr;8:574–581. doi: 10.1016/s0022-2836(64)80012-7. [DOI] [PubMed] [Google Scholar]
  19. Helentjaris T., Ehrenfeld E. Inhibition of host cell protein synthesis by UV-inactivated poliovirus. J Virol. 1977 Jan;21(1):259–267. doi: 10.1128/jvi.21.1.259-267.1977. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hewlett M. J., Rose J. K., Baltimore D. 5'-terminal structure of poliovirus polyribosomal RNA is pUp. Proc Natl Acad Sci U S A. 1976 Feb;73(2):327–330. doi: 10.1073/pnas.73.2.327. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lee K. A., Edery I., Hanecak R., Wimmer E., Sonenberg N. Poliovirus protease 3C (P3-7c) does not cleave P220 of the eucaryotic mRNA cap-binding protein complex. J Virol. 1985 Aug;55(2):489–493. doi: 10.1128/jvi.55.2.489-493.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Lee K. A., Edery I., Sonenberg N. Isolation and structural characterization of cap-binding proteins from poliovirus-infected HeLa cells. J Virol. 1985 May;54(2):515–524. doi: 10.1128/jvi.54.2.515-524.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Lee K. A., Sonenberg N. Inactivation of cap-binding proteins accompanies the shut-off of host protein synthesis by poliovirus. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3447–3451. doi: 10.1073/pnas.79.11.3447. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. 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]
  25. 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]
  26. Lockard R. E., Lane C. Requirement for 7-methylguanosine in translation of globin mRNA in vivo. Nucleic Acids Res. 1978 Sep;5(9):3237–3247. doi: 10.1093/nar/5.9.3237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Nomoto A., Lee Y. F., Wimmer E. The 5' end of poliovirus mRNA is not capped with m7G(5')ppp(5')Np. Proc Natl Acad Sci U S A. 1976 Feb;73(2):375–380. doi: 10.1073/pnas.73.2.375. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Pelletier J., Sonenberg N. Insertion mutagenesis to increase secondary structure within the 5' noncoding region of a eukaryotic mRNA reduces translational efficiency. Cell. 1985 Mar;40(3):515–526. doi: 10.1016/0092-8674(85)90200-4. [DOI] [PubMed] [Google Scholar]
  29. Penman S., Summers D. Effects on host cell metabolism following synchronous infection with poliovirus. Virology. 1965 Dec;27(4):614–620. doi: 10.1016/0042-6822(65)90187-x. [DOI] [PubMed] [Google Scholar]
  30. Ray B. K., Lawson T. G., Kramer J. C., Cladaras M. H., Grifo J. A., Abramson R. D., Merrick W. C., Thach R. E. ATP-dependent unwinding of messenger RNA structure by eukaryotic initiation factors. J Biol Chem. 1985 Jun 25;260(12):7651–7658. [PubMed] [Google Scholar]
  31. Rose J. K., Trachsel H., Leong K., Baltimore D. Inhibition of translation by poliovirus: inactivation of a specific initiation factor. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2732–2736. doi: 10.1073/pnas.75.6.2732. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. 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]
  33. Sonenberg N., Guertin D., Lee K. A. Capped mRNAs with reduced secondary structure can function in extracts from poliovirus-infected cells. Mol Cell Biol. 1982 Dec;2(12):1633–1638. doi: 10.1128/mcb.2.12.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Sonenberg N., Morgan M. A., Merrick W. C., Shatkin A. J. A polypeptide in eukaryotic initiation factors that crosslinks specifically to the 5'-terminal cap in mRNA. Proc Natl Acad Sci U S A. 1978 Oct;75(10):4843–4847. doi: 10.1073/pnas.75.10.4843. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Sonenberg N. Regulation of translation by poliovirus. Adv Virus Res. 1987;33:175–204. doi: 10.1016/s0065-3527(08)60318-8. [DOI] [PubMed] [Google Scholar]
  36. Sonenberg N., Rupprecht K. M., Hecht S. M., Shatkin A. J. Eukaryotic mRNA cap binding protein: purification by affinity chromatography on sepharose-coupled m7GDP. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4345–4349. doi: 10.1073/pnas.76.9.4345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. 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]
  38. 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]
  39. Toyoda H., Nicklin M. J., Murray M. G., Anderson C. W., Dunn J. J., Studier F. W., Wimmer E. A second virus-encoded proteinase involved in proteolytic processing of poliovirus polyprotein. Cell. 1986 Jun 6;45(5):761–770. doi: 10.1016/0092-8674(86)90790-7. [DOI] [PubMed] [Google Scholar]
  40. Van Hoof L., Berghe D. A., Hatfield G. M., Vlietinck A. J. Plant Antiviral Agents; VI.1 3-Methoxyflavones as Potent Inhibitors of Viral-Induced Block of Cell Synthesis. Planta Med. 1984 Dec;50(6):513–517. doi: 10.1055/s-2007-969786. [DOI] [PubMed] [Google Scholar]
  41. Van Hoof L., Vanden Berghe D. A., Hatfield G. M., Vlietinck A. J. Plant antiviral agents; V. 3-Methoxyflavones as potent inhibitors of viral-induced block of cell synthesis. Planta Med. 1984 Dec;50(6):513–517. [PubMed] [Google Scholar]
  42. Weber L. A., Hickey E. D., Nuss D. L., Baglioni C. 5'-Terminal 7-methylguanosine and mRNA function: influence of potassium concentration on translation in vitro. Proc Natl Acad Sci U S A. 1977 Aug;74(8):3254–3258. doi: 10.1073/pnas.74.8.3254. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES