Abstract
Translation of vesicular stomatitis virus (VSV) mRNA, like host mRNA translation, is inhibited in cells infected with poliovirus. To study the mechanism of poliovirus-induced inhibition of protein synthesis, we prepared extracts from poliovirus-infected and uninfected HeLa cells. Poliovirus mRNA was translated in lysates from both infected and uninfected cells, while VSV mRNA was translated only in the lysate from uninfected cells. Addition of purified translation initiation factors to the extract from infected cells showed that one factor, eIF-4B, could restore VSV mRNA translation in the infected lysate, but did not increase poliovirus mRNA translation. Further experiments involving translation of VSV mRNA in mixed extracts from poliovirus-infected and uninfected cells showed (i) that there was not an excess of an inhibitor of VSV mRNA translation in the infected lysate, but (ii) that an acitivity that caused a slow inactivation of eIF-4B was present in the infected lysate. Inactivation of eIF-4B appears to be the mechanism by which poliovirus infection causes a selective inhibition of translation.
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- Abreu S. L., Lucas-Lenard J. Cellular protein synthesis shutoff by mengovirus: translation of nonviral and viral mRNA's in extracts from uninfected and infected Ehrlich ascites tumor cells. J Virol. 1976 Apr;18(1):182–194. doi: 10.1128/jvi.18.1.182-194.1976. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Balanian R. Structural and functional alterations in cultured cells infected with cytocidal viruses. Prog Med Virol. 1975;19:40–83. [PubMed] [Google Scholar]
- Baltimore D., Girard M., Darnell J. E. Aspects of the synthesis of poliovirus RNA and the formation of virus particles. Virology. 1966 Jun;29(2):179–189. doi: 10.1016/0042-6822(66)90024-9. [DOI] [PubMed] [Google Scholar]
- Both G. W., Moyer S. A., Banerjee A. K. Translation and identification of the mRNA species synthesized in vitro by the virion-associated RNA polymerase of vesicular stomatitis virus. Proc Natl Acad Sci U S A. 1975 Jan;72(1):274–278. doi: 10.1073/pnas.72.1.274. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cleveland D. W., Fischer S. G., Kirschner M. W., Laemmli U. K. Peptide mapping by limited proteolysis in sodium dodecyl sulfate and analysis by gel electrophoresis. J Biol Chem. 1977 Feb 10;252(3):1102–1106. [PubMed] [Google Scholar]
- Doyle M., Holland J. J. Virus-induced interference in heterologously infected HeLa cells. J Virol. 1972 Jan;9(1):22–28. doi: 10.1128/jvi.9.1.22-28.1972. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ehrenfeld E., Lund H. Untranslated vesicular stomatitis virus messenger RNA after poliovirus infection. Virology. 1977 Jul 15;80(2):297–308. doi: 10.1016/s0042-6822(77)80006-8. [DOI] [PubMed] [Google Scholar]
- 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]
- Flanegan J. B., Petterson R. F., Ambros V., Hewlett N. J., Baltimore D. Covalent linkage of a protein to a defined nucleotide sequence at the 5'-terminus of virion and replicative intermediate RNAs of poliovirus. Proc Natl Acad Sci U S A. 1977 Mar;74(3):961–965. doi: 10.1073/pnas.74.3.961. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Golini F., Thach S. S., Birge C. H., Safer B., Merrick W. C., Thach R. E. Competition between cellular and viral mRNAs in vitro is regulated by a messenger discriminatory initiation factor. Proc Natl Acad Sci U S A. 1976 Sep;73(9):3040–3044. doi: 10.1073/pnas.73.9.3040. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Kaufmann Y., Goldstein E., Penman S. Poliovirus-induced inhibition of polypeptide initiation in vitro on native polyribosomes. Proc Natl Acad Sci U S A. 1976 Jun;73(6):1834–1838. doi: 10.1073/pnas.73.6.1834. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knipe D., Rose J. K., Lodish H. F. Translation of individual species of vesicular stomatitis viral mRNA. J Virol. 1975 Apr;15(4):1004–1011. doi: 10.1128/jvi.15.4.1004-1011.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Laskey R. A., Mills A. D. Quantitative film detection of 3H and 14C in polyacrylamide gels by fluorography. Eur J Biochem. 1975 Aug 15;56(2):335–341. doi: 10.1111/j.1432-1033.1975.tb02238.x. [DOI] [PubMed] [Google Scholar]
- Lawrence C., Thach R. E. Encephalomyocarditis virus infection of mouse plasmacytoma cells. I. Inhibition of cellular protein synthesis. J Virol. 1974 Sep;14(3):598–610. doi: 10.1128/jvi.14.3.598-610.1974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lee Y. F., Nomoto A., Detjen B. M., Wimmer E. A protein covalently linked to poliovirus genome RNA. Proc Natl Acad Sci U S A. 1977 Jan;74(1):59–63. doi: 10.1073/pnas.74.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leibowitz R., Penman S. Regulation of protein synthesis in HeLa cells. 3. Inhibition during poliovirus infection. J Virol. 1971 Nov;8(5):661–668. doi: 10.1128/jvi.8.5.661-668.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Pelham H. R., Jackson R. J. An efficient mRNA-dependent translation system from reticulocyte lysates. Eur J Biochem. 1976 Aug 1;67(1):247–256. doi: 10.1111/j.1432-1033.1976.tb10656.x. [DOI] [PubMed] [Google Scholar]
- Rose J. K., Lodish H. F. Translation in vitro of vesicular stomatitis virus mRNA lacking 5'-terminal 7-methylguanosine. Nature. 1976 Jul 1;262(5563):32–37. doi: 10.1038/262032a0. [DOI] [PubMed] [Google Scholar]
- Schreier M. H., Erni B., Staehelin T. Initiation of mammalian protein synthesis. I. Purification and characterization of seven initiation factors. J Mol Biol. 1977 Nov;116(4):727–753. doi: 10.1016/0022-2836(77)90268-6. [DOI] [PubMed] [Google Scholar]
- Shafritz D. A., Weinstein J. A., Safer B., Merrick W. C., Weber L. A., Hickey E. D., Baglioni C. Evidence for role of m7G5'-phosphate group in recognition of eukaryotic mRNA by initiation factor IF-M3. Nature. 1976 May 27;261(5558):291–294. doi: 10.1038/261291a0. [DOI] [PubMed] [Google Scholar]
- Shatkin A. J. Capping of eucaryotic mRNAs. Cell. 1976 Dec;9(4 Pt 2):645–653. doi: 10.1016/0092-8674(76)90128-8. [DOI] [PubMed] [Google Scholar]
- Steiner-Pryor A., Cooper P. D. Temperature-sensitive poliovirus mutants defective in repression of host protein synthesis are also defective in structural protein. J Gen Virol. 1973 Nov;21(2):215–225. doi: 10.1099/0022-1317-21-2-215. [DOI] [PubMed] [Google Scholar]
- Taber R., Rekosh D., Baltimore D. Effect of pactamycin on synthesis of poliovirus proteins: a method for genetic mapping. J Virol. 1971 Oct;8(4):395–401. doi: 10.1128/jvi.8.4.395-401.1971. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Trachsel H., Erni B., Schreier M. H., Staehelin T. Initiation of mammalian protein synthesis. II. The assembly of the initiation complex with purified initiation factors. J Mol Biol. 1977 Nov;116(4):755–767. doi: 10.1016/0022-2836(77)90269-8. [DOI] [PubMed] [Google Scholar]
- Villa-Komaroff L., McDowell M., Baltimore D., Lodish H. F. Translation of reovirus mRNA, poliovirus RNA and bacteriophage Qbeta RNA in cell-free extracts of mammalian cells. Methods Enzymol. 1974;30:709–723. doi: 10.1016/0076-6879(74)30068-7. [DOI] [PubMed] [Google Scholar]