Abstract
Viral protein synthesis in poliovirus infected cells was found to be influenced by mutations in part of the viral 5'-non-coding region (NCR) in a temperature dependent manner. At elevated temperatures these mutations resulted in virus titre reductions that allowed selection of revertant viruses. Some revertants were found to have retained the 5'-NCR mutations but had compensating mutations in the 2A protease gene that were responsible for the suppression of the temperature sensitive phenotypes. The mutations in 2A enhanced viral protein synthesis at a stage when cap dependent translation was already abolished, suggesting that the virally encoded protein 2A is directly involved in the process of cap independent translation in addition to its role in abolishing cap dependent translation.
Full text
PDF



Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bazan J. F., Fletterick R. J. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proc Natl Acad Sci U S A. 1988 Nov;85(21):7872–7876. doi: 10.1073/pnas.85.21.7872. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Bonneau A. M., Sonenberg N. Involvement of the 24-kDa cap-binding protein in regulation of protein synthesis in mitosis. J Biol Chem. 1987 Aug 15;262(23):11134–11139. [PubMed] [Google Scholar]
- Hambidge S. J., Sarnow P. Translational enhancement of the poliovirus 5' noncoding region mediated by virus-encoded polypeptide 2A. Proc Natl Acad Sci U S A. 1992 Nov 1;89(21):10272–10276. doi: 10.1073/pnas.89.21.10272. [DOI] [PMC free article] [PubMed] [Google Scholar]
- La Monica N., Racaniello V. R. Differences in replication of attenuated and neurovirulent polioviruses in human neuroblastoma cell line SH-SY5Y. J Virol. 1989 May;63(5):2357–2360. doi: 10.1128/jvi.63.5.2357-2360.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lamphear B. J., Panniers R. Heat shock impairs the interaction of cap-binding protein complex with 5' mRNA cap. J Biol Chem. 1991 Feb 15;266(5):2789–2794. [PubMed] [Google Scholar]
- Macadam A. J., Ferguson G., Arnold C., Minor P. D. An assembly defect as a result of an attenuating mutation in the capsid proteins of the poliovirus type 3 vaccine strain. J Virol. 1991 Oct;65(10):5225–5231. doi: 10.1128/jvi.65.10.5225-5231.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Macadam A. J., Ferguson G., Burlison J., Stone D., Skuce R., Almond J. W., Minor P. D. Correlation of RNA secondary structure and attenuation of Sabin vaccine strains of poliovirus in tissue culture. Virology. 1992 Aug;189(2):415–422. doi: 10.1016/0042-6822(92)90565-7. [DOI] [PubMed] [Google Scholar]
- Macadam A. J., Pollard S. R., Ferguson G., Dunn G., Skuce R., Almond J. W., Minor P. D. The 5' noncoding region of the type 2 poliovirus vaccine strain contains determinants of attenuation and temperature sensitivity. Virology. 1991 Apr;181(2):451–458. doi: 10.1016/0042-6822(91)90877-e. [DOI] [PubMed] [Google Scholar]
- Macejak D. G., Sarnow P. Internal initiation of translation mediated by the 5' leader of a cellular mRNA. Nature. 1991 Sep 5;353(6339):90–94. doi: 10.1038/353090a0. [DOI] [PubMed] [Google Scholar]
- Minor P. D., Dunn G. The effect of sequences in the 5' non-coding region on the replication of polioviruses in the human gut. J Gen Virol. 1988 May;69(Pt 5):1091–1096. doi: 10.1099/0022-1317-69-5-1091. [DOI] [PubMed] [Google Scholar]
- Minor P. D. The molecular biology of poliovaccines. J Gen Virol. 1992 Dec;73(Pt 12):3065–3077. doi: 10.1099/0022-1317-73-12-3065. [DOI] [PubMed] [Google Scholar]
- Pelletier J., Sonenberg N. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature. 1988 Jul 28;334(6180):320–325. doi: 10.1038/334320a0. [DOI] [PubMed] [Google Scholar]
- Percy N., Belsham G. J., Brangwyn J. K., Sullivan M., Stone D. M., Almond J. W. Intracellular modifications induced by poliovirus reduce the requirement for structural motifs in the 5' noncoding region of the genome involved in internal initiation of protein synthesis. J Virol. 1992 Mar;66(3):1695–1701. doi: 10.1128/jvi.66.3.1695-1701.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Pollard S. R., Dunn G., Cammack N., Minor P. D., Almond J. W. Nucleotide sequence of a neurovirulent variant of the type 2 oral poliovirus vaccine. J Virol. 1989 Nov;63(11):4949–4951. doi: 10.1128/jvi.63.11.4949-4951.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Query C. C., Bentley R. C., Keene J. D. A common RNA recognition motif identified within a defined U1 RNA binding domain of the 70K U1 snRNP protein. Cell. 1989 Apr 7;57(1):89–101. doi: 10.1016/0092-8674(89)90175-x. [DOI] [PubMed] [Google Scholar]
- Skinner M. A., Racaniello V. R., Dunn G., Cooper J., Minor P. D., Almond J. W. New model for the secondary structure of the 5' non-coding RNA of poliovirus is supported by biochemical and genetic data that also show that RNA secondary structure is important in neurovirulence. J Mol Biol. 1989 May 20;207(2):379–392. doi: 10.1016/0022-2836(89)90261-1. [DOI] [PubMed] [Google Scholar]
- Svitkin Y. V., Cammack N., Minor P. D., Almond J. W. Translation deficiency of the Sabin type 3 poliovirus genome: association with an attenuating mutation C472----U. Virology. 1990 Mar;175(1):103–109. doi: 10.1016/0042-6822(90)90190-3. [DOI] [PubMed] [Google Scholar]
- Yu S. F., Lloyd R. E. Identification of essential amino acid residues in the functional activity of poliovirus 2A protease. Virology. 1991 Jun;182(2):615–625. doi: 10.1016/0042-6822(91)90602-8. [DOI] [PubMed] [Google Scholar]
- van der Werf S., Bradley J., Wimmer E., Studier F. W., Dunn J. J. Synthesis of infectious poliovirus RNA by purified T7 RNA polymerase. Proc Natl Acad Sci U S A. 1986 Apr;83(8):2330–2334. doi: 10.1073/pnas.83.8.2330. [DOI] [PMC free article] [PubMed] [Google Scholar]