Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1992 May;66(5):3194–3197. doi: 10.1128/jvi.66.5.3194-3197.1992

A mutation present in the amino terminus of Sabin 3 poliovirus VP1 protein is attenuating.

J M Tatem 1, C Weeks-Levy 1, A Georgiu 1, S J DiMichele 1, E J Gorgacz 1, V R Racaniello 1, F R Cano 1, S J Mento 1
PMCID: PMC241086  PMID: 1313923

Abstract

The attenuated phenotype of Sabin 3 poliovirus compared with its neurovirulent progenitor strain has been largely accounted for by mutations in the genome at positions 472 and 2034 (G. D. Westrop, K. A. Wareham, D. M. A. Evans, G. Dunn, P. D. Minor, D. I. Magrath, F. Taffs, S. Marsden, M. A. Skinner, G. C. Schild, and J. W. Almond, J. Virol. 63:1338-1344, 1989). By sequencing vaccine virus RNA, we recently identified another Sabin 3-specific mutation at position 2493 (U----C), which predicts an Ile----Thr change at the sixth residue of VP1 (C. Weeks-Levy, J. M. Tatem, S. J. DiMichele, W. Waterfield, A. F. Georgiu, and S. J. Mento, Virology 185:934-937, 1991). Viruses generated by using cDNAs which represent the vaccine sequence (LED3) and a derivative (VR318) possessing a single base change to the wild-type nucleotide (U) at 2493 were used to determine the impact of the 2493 mutation on virus phenotype. The VP1 proteins of LED3 and VR318 viruses were distinguishable by denaturing electrophoretic analysis. LED3 produced smaller plaques in Vero cells than VR318 virus did. Neurovirulence testing of these cDNA-derived viruses in monkeys demonstrated that the 2493 mutation in LED3 virus is attenuating.

Full text

PDF
3194

Images in this article

3195Image
on p.3195
3195Image
on p.3195

Selected References

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

  1. Albrecht P., Enterline J. C., Boone E. J., Klutch M. J. Poliovirus and polio antibody assay in HEp-2 and Vero cell cultures. J Biol Stand. 1983 Apr;11(2):91–97. doi: 10.1016/s0092-1157(83)80031-6. [DOI] [PubMed] [Google Scholar]
  2. Chumakov K. M., Powers L. B., Noonan K. E., Roninson I. B., Levenbook I. S. Correlation between amount of virus with altered nucleotide sequence and the monkey test for acceptability of oral poliovirus vaccine. Proc Natl Acad Sci U S A. 1991 Jan 1;88(1):199–203. doi: 10.1073/pnas.88.1.199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Domingo E. RNA virus evolution and the control of viral disease. Prog Drug Res. 1989;33:93–133. doi: 10.1007/978-3-0348-9146-2_5. [DOI] [PubMed] [Google Scholar]
  4. Dunn G., Begg N. T., Cammack N., Minor P. D. Virus excretion and mutation by infants following primary vaccination with live oral poliovaccine from two sources. J Med Virol. 1990 Oct;32(2):92–95. doi: 10.1002/jmv.1890320205. [DOI] [PubMed] [Google Scholar]
  5. Fricks C. E., Hogle J. M. Cell-induced conformational change in poliovirus: externalization of the amino terminus of VP1 is responsible for liposome binding. J Virol. 1990 May;64(5):1934–1945. doi: 10.1128/jvi.64.5.1934-1945.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hogle J. M., Chow M., Filman D. J. Three-dimensional structure of poliovirus at 2.9 A resolution. Science. 1985 Sep 27;229(4720):1358–1365. doi: 10.1126/science.2994218. [DOI] [PubMed] [Google Scholar]
  7. Kew O. M., Nottay B. K., Hatch M. H., Nakano J. H., Obijeski J. F. Multiple genetic changes can occur in the oral poliovaccines upon replication in humans. J Gen Virol. 1981 Oct;56(Pt 2):337–347. doi: 10.1099/0022-1317-56-2-337. [DOI] [PubMed] [Google Scholar]
  8. Kew O. M., Pallansch M. A., Omilianowski D. R., Rueckert R. R. Changes in three of the four coat proteins of oral polio vaccine strain derived from type 1 poliovirus. J Virol. 1980 Jan;33(1):256–263. doi: 10.1128/jvi.33.1.256-263.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Kirkegaard K. Mutations in VP1 of poliovirus specifically affect both encapsidation and release of viral RNA. J Virol. 1990 Jan;64(1):195–206. doi: 10.1128/jvi.64.1.195-206.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kohara M., Abe S., Kuge S., Semler B. L., Komatsu T., Arita M., Itoh H., Nomoto A. An infectious cDNA clone of the poliovirus Sabin strain could be used as a stable repository and inoculum for the oral polio live vaccine. Virology. 1986 May;151(1):21–30. doi: 10.1016/0042-6822(86)90100-5. [DOI] [PubMed] [Google Scholar]
  11. 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]
  12. Moss E. G., O'Neill R. E., Racaniello V. R. Mapping of attenuating sequences of an avirulent poliovirus type 2 strain. J Virol. 1989 May;63(5):1884–1890. doi: 10.1128/jvi.63.5.1884-1890.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Nakano J. H., Hatch M. H., Thieme M. L., Nottay B. Parameters for differentiating vaccine-derived and wild poliovirus strains. Prog Med Virol. 1978;24:178–206. [PubMed] [Google Scholar]
  14. Racaniello V. R. Poliovirus neurovirulence. Adv Virus Res. 1988;34:217–246. doi: 10.1016/s0065-3527(08)60519-9. [DOI] [PubMed] [Google Scholar]
  15. Ren R. B., Moss E. G., Racaniello V. R. Identification of two determinants that attenuate vaccine-related type 2 poliovirus. J Virol. 1991 Mar;65(3):1377–1382. doi: 10.1128/jvi.65.3.1377-1382.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Stanway G., Cann A. J., Hauptmann R., Hughes P., Clarke L. D., Mountford R. C., Minor P. D., Schild G. C., Almond J. W. The nucleotide sequence of poliovirus type 3 leon 12 a1b: comparison with poliovirus type 1. Nucleic Acids Res. 1983 Aug 25;11(16):5629–5643. doi: 10.1093/nar/11.16.5629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Stanway G., Hughes P. J., Mountford R. C., Reeve P., Minor P. D., Schild G. C., Almond J. W. Comparison of the complete nucleotide sequences of the genomes of the neurovirulent poliovirus P3/Leon/37 and its attenuated Sabin vaccine derivative P3/Leon 12a1b. Proc Natl Acad Sci U S A. 1984 Mar;81(5):1539–1543. doi: 10.1073/pnas.81.5.1539. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Swanson S. K., Mento S. J., Weeks-Levy C., Brock B. D., Kowal K. J., Wallace R. E., Ritchey M. B., Cano F. R. Characterization of Vero cells. J Biol Stand. 1988 Oct;16(4):311–320. doi: 10.1016/0092-1157(88)90019-4. [DOI] [PubMed] [Google Scholar]
  19. Tatem J. M., Weeks-Levy C., Mento S. J., DiMichele S. J., Georgiu A., Waterfield W. F., Sheip B., Costalas C., Davies T., Ritchey M. B. Oral poliovirus vaccine in the United States: molecular characterization of Sabin type 3 after replication in the gut of vaccinees. J Med Virol. 1991 Oct;35(2):101–109. doi: 10.1002/jmv.1890350206. [DOI] [PubMed] [Google Scholar]
  20. Toyoda H., Kohara M., Kataoka Y., Suganuma T., Omata T., Imura N., Nomoto A. Complete nucleotide sequences of all three poliovirus serotype genomes. Implication for genetic relationship, gene function and antigenic determinants. J Mol Biol. 1984 Apr 25;174(4):561–585. doi: 10.1016/0022-2836(84)90084-6. [DOI] [PubMed] [Google Scholar]
  21. Weeks-Levy C., Tatem J. M., DiMichele S. J., Waterfield W., Georgiu A. F., Mento S. J. Identification and characterization of a new base substitution in the vaccine strain of Sabin 3 poliovirus. Virology. 1991 Dec;185(2):934–937. doi: 10.1016/0042-6822(91)90576-w. [DOI] [PubMed] [Google Scholar]
  22. Westrop G. D., Wareham K. A., Evans D. M., Dunn G., Minor P. D., Magrath D. I., Taffs F., Marsden S., Skinner M. A., Schild G. C. Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine. J Virol. 1989 Mar;63(3):1338–1344. doi: 10.1128/jvi.63.3.1338-1344.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. 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]

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

RESOURCES