Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1989 May;63(5):1884–1890. doi: 10.1128/jvi.63.5.1884-1890.1989

Mapping of attenuating sequences of an avirulent poliovirus type 2 strain.

E G Moss 1, R E O'Neill 1, V R Racaniello 1
PMCID: PMC250599  PMID: 2539491

Abstract

A mouse model for poliomyelitis was used to identify genomic sequences that attenuate neurovirulence of poliovirus strain P2/P712. This type 2 strain is avirulent in primates and mice yet grows as well as virulent strains in cell culture. The approach used was to exchange portions of the genome of the mouse-virulent P2/Lansing strain with the corresponding region from P2/P712 to identify sequences that could attenuate Lansing neurovirulence in mice. A full-length infectious cDNA of P2/P712 was assembled and used to construct recombinants between P2/P712 and P2/Lansing. The results of neurovirulence testing of 11 recombinants indicated that strong attenuating determinants are located in the 5' noncoding region of P2/P712 and a region encoding capsid protein VP1 and 2Apro, 2B, and part of 2C. An attenuating determinant was further localized to between nucleotides 456 and 628 of P2/P712. A third sequence from P2/P712, nucleotides 752 to 2268, encoding VP4, VP2, and part of VP3, was weakly attenuating. The sequence from nucleotide 4454, approximately halfway through the 2C-coding region, to the end of the P2/P712 genome did not contain attenuating determinants. Nucleotide sequence analysis revealed that P2/P712 differs from the type 2 Sabin vaccine strain by only 22 nucleotides. Six differences lead to amino acid changes in the coding region, and four differences are in the 5' noncoding region. These studies show that, like the type 1 and type 3 Sabin vaccine strains, the attenuated type 2 strain P712 contains multiple attenuating sequences, including strongly attenuating sequences in the 5' noncoding region of the genome.

Full text

PDF
1884

Selected References

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

  1. Cann A. J., Stanway G., Hughes P. J., Minor P. D., Evans D. M., Schild G. C., Almond J. W. Reversion to neurovirulence of the live-attenuated Sabin type 3 oral poliovirus vaccine. Nucleic Acids Res. 1984 Oct 25;12(20):7787–7792. doi: 10.1093/nar/12.20.7787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Hanahan D. Studies on transformation of Escherichia coli with plasmids. J Mol Biol. 1983 Jun 5;166(4):557–580. doi: 10.1016/s0022-2836(83)80284-8. [DOI] [PubMed] [Google Scholar]
  3. Jubelt B., Gallez-Hawkins G., Narayan O., Johnson R. T. Pathogenesis of human poliovirus infection in mice. I. Clinical and pathological studies. J Neuropathol Exp Neurol. 1980 Mar;39(2):138–148. doi: 10.1097/00005072-198003000-00003. [DOI] [PubMed] [Google Scholar]
  4. Kohara M., Omata T., Kameda A., Semler B. L., Itoh H., Wimmer E., Nomoto A. In vitro phenotypic markers of a poliovirus recombinant constructed from infectious cDNA clones of the neurovirulent Mahoney strain and the attenuated Sabin 1 strain. J Virol. 1985 Mar;53(3):786–792. doi: 10.1128/jvi.53.3.786-792.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. La Monica N., Almond J. W., Racaniello V. R. A mouse model for poliovirus neurovirulence identifies mutations that attenuate the virus for humans. J Virol. 1987 Sep;61(9):2917–2920. doi: 10.1128/jvi.61.9.2917-2920.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. La Monica N., Kupsky W. J., Racaniello V. R. Reduced mouse neurovirulence of poliovirus type 2 Lansing antigenic variants selected with monoclonal antibodies. Virology. 1987 Dec;161(2):429–437. doi: 10.1016/0042-6822(87)90136-X. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. La Monica N., Meriam C., Racaniello V. R. Mapping of sequences required for mouse neurovirulence of poliovirus type 2 Lansing. J Virol. 1986 Feb;57(2):515–525. doi: 10.1128/jvi.57.2.515-525.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Martin A., Wychowski C., Couderc T., Crainic R., Hogle J., Girard M. Engineering a poliovirus type 2 antigenic site on a type 1 capsid results in a chimaeric virus which is neurovirulent for mice. EMBO J. 1988 Sep;7(9):2839–2847. doi: 10.1002/j.1460-2075.1988.tb03140.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. 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]
  10. Murray M. G., Bradley J., Yang X. F., Wimmer E., Moss E. G., Racaniello V. R. Poliovirus host range is determined by a short amino acid sequence in neutralization antigenic site I. Science. 1988 Jul 8;241(4862):213–215. doi: 10.1126/science.2838906. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Nkowane B. M., Wassilak S. G., Orenstein W. A., Bart K. J., Schonberger L. B., Hinman A. R., Kew O. M. Vaccine-associated paralytic poliomyelitis. United States: 1973 through 1984. JAMA. 1987 Mar 13;257(10):1335–1340. [PubMed] [Google Scholar]
  12. Pelletier J., Kaplan G., Racaniello V. R., Sonenberg N. Cap-independent translation of poliovirus mRNA is conferred by sequence elements within the 5' noncoding region. Mol Cell Biol. 1988 Mar;8(3):1103–1112. doi: 10.1128/mcb.8.3.1103. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Pelletier J., Kaplan G., Racaniello V. R., Sonenberg N. Translational efficiency of poliovirus mRNA: mapping inhibitory cis-acting elements within the 5' noncoding region. J Virol. 1988 Jul;62(7):2219–2227. doi: 10.1128/jvi.62.7.2219-2227.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. 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]
  15. Racaniello V. R., Baltimore D. Cloned poliovirus complementary DNA is infectious in mammalian cells. Science. 1981 Nov 20;214(4523):916–919. doi: 10.1126/science.6272391. [DOI] [PubMed] [Google Scholar]
  16. Racaniello V. R., Baltimore D. Molecular cloning of poliovirus cDNA and determination of the complete nucleotide sequence of the viral genome. Proc Natl Acad Sci U S A. 1981 Aug;78(8):4887–4891. doi: 10.1073/pnas.78.8.4887. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Racaniello V. R., Meriam C. Poliovirus temperature-sensitive mutant containing a single nucleotide deletion in the 5'-noncoding region of the viral RNA. Virology. 1986 Dec;155(2):498–507. doi: 10.1016/0042-6822(86)90211-4. [DOI] [PubMed] [Google Scholar]
  18. SABIN A. B. Present status of attenuated live-virus poliomyelitis vaccine. J Am Med Assoc. 1956 Dec 29;162(18):1589–1596. doi: 10.1001/jama.1956.02970350005002. [DOI] [PubMed] [Google Scholar]
  19. Svitkin Y. V., Maslova S. V., Agol V. I. The genomes of attenuated and virulent poliovirus strains differ in their in vitro translation efficiencies. Virology. 1985 Dec;147(2):243–252. doi: 10.1016/0042-6822(85)90127-8. [DOI] [PubMed] [Google Scholar]
  20. Ticehurst J. R., Racaniello V. R., Baroudy B. M., Baltimore D., Purcell R. H., Feinstone S. M. Molecular cloning and characterization of hepatitis A virus cDNA. Proc Natl Acad Sci U S A. 1983 Oct;80(19):5885–5889. doi: 10.1073/pnas.80.19.5885. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. 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]
  22. Trono D., Pelletier J., Sonenberg N., Baltimore D. Translation in mammalian cells of a gene linked to the poliovirus 5' noncoding region. Science. 1988 Jul 22;241(4864):445–448. doi: 10.1126/science.2839901. [DOI] [PubMed] [Google Scholar]
  23. Vieira J., Messing J. The pUC plasmids, an M13mp7-derived system for insertion mutagenesis and sequencing with synthetic universal primers. Gene. 1982 Oct;19(3):259–268. doi: 10.1016/0378-1119(82)90015-4. [DOI] [PubMed] [Google Scholar]
  24. Vogelstein B., Gillespie D. Preparative and analytical purification of DNA from agarose. Proc Natl Acad Sci U S A. 1979 Feb;76(2):615–619. doi: 10.1073/pnas.76.2.615. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
  26. 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