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. 1994 Feb;68(2):681–688. doi: 10.1128/jvi.68.2.681-688.1994

Transgenic mice carrying the human poliovirus receptor: new animal models for study of poliovirus neurovirulence.

H Horie 1, S Koike 1, T Kurata 1, Y Sato-Yoshida 1, I Ise 1, Y Ota 1, S Abe 1, K Hioki 1, H Kato 1, C Taya 1, et al.
PMCID: PMC236503  PMID: 8289371

Abstract

Recombinant viruses between the virulent Mahoney and attenuated Sabin 1 strains of poliovirus type 1 were subjected to neurovirulence tests using a transgenic (Tg) mouse line, ICR-PVRTg1, that carried the human poliovirus receptor gene. The Tg mice were inoculated intracerebrally with these recombinant viruses and observed for clinical signs, histopathological lesions, and viral antigens as parameters of neurovirulence of the viruses. These parameters observed in the Tg mice were different for different inoculated viruses. Dose-dependent incidences of paralysis and of death were observed in the Tg mice inoculated with any viruses used. This indicates that values of 50% lethal dose are useful to score a wide range of neurovirulence of poliovirus. The neurovirulence of individual viruses estimated by the Tg mouse model had a strong correlation with those estimated by monkey model. Consequently, the mouse tests identified the neurovirulence determinants on the genome of poliovirus that had been identified by monkey tests. In addition, the mouse tests revealed new neurovirulence determinants, that is, different nucleotides between the two strains at positions 189 and 21 and/or 935 in the 5'-proximal 1,122 nucleotides. The Tg mice used in this study may be suitable for replacing monkeys for investigating poliovirus neurovirulence.

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Selected References

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  1. Christodoulou C., Colbere-Garapin F., Macadam A., Taffs L. F., Marsden S., Minor P., Horaud F. Mapping of mutations associated with neurovirulence in monkeys infected with Sabin 1 poliovirus revertants selected at high temperature. J Virol. 1990 Oct;64(10):4922–4929. doi: 10.1128/jvi.64.10.4922-4929.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Evans D. M., Dunn G., Minor P. D., Schild G. C., Cann A. J., Stanway G., Almond J. W., Currey K., Maizel J. V., Jr Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature. 1985 Apr 11;314(6011):548–550. doi: 10.1038/314548a0. [DOI] [PubMed] [Google Scholar]
  3. Higuchi R. G., Ochman H. Production of single-stranded DNA templates by exonuclease digestion following the polymerase chain reaction. Nucleic Acids Res. 1989 Jul 25;17(14):5865–5865. doi: 10.1093/nar/17.14.5865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. KLUVER H., BARRERA E. A method for the combined staining of cells and fibers in the nervous system. J Neuropathol Exp Neurol. 1953 Oct;12(4):400–403. doi: 10.1097/00005072-195312040-00008. [DOI] [PubMed] [Google Scholar]
  5. Kawamura N., Kohara M., Abe S., Komatsu T., Tago K., Arita M., Nomoto A. Determinants in the 5' noncoding region of poliovirus Sabin 1 RNA that influence the attenuation phenotype. J Virol. 1989 Mar;63(3):1302–1309. doi: 10.1128/jvi.63.3.1302-1309.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Kitamura N., Semler B. L., Rothberg P. G., Larsen G. R., Adler C. J., Dorner A. J., Emini E. A., Hanecak R., Lee J. J., van der Werf S. Primary structure, gene organization and polypeptide expression of poliovirus RNA. Nature. 1981 Jun 18;291(5816):547–553. doi: 10.1038/291547a0. [DOI] [PubMed] [Google Scholar]
  7. Kohara M., Abe S., Komatsu T., Tago K., Arita M., Nomoto A. A recombinant virus between the Sabin 1 and Sabin 3 vaccine strains of poliovirus as a possible candidate for a new type 3 poliovirus live vaccine strain. J Virol. 1988 Aug;62(8):2828–2835. doi: 10.1128/jvi.62.8.2828-2835.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. 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]
  9. Koike S., Horie H., Ise I., Okitsu A., Yoshida M., Iizuka N., Takeuchi K., Takegami T., Nomoto A. The poliovirus receptor protein is produced both as membrane-bound and secreted forms. EMBO J. 1990 Oct;9(10):3217–3224. doi: 10.1002/j.1460-2075.1990.tb07520.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Koike S., Taya C., Kurata T., Abe S., Ise I., Yonekawa H., Nomoto A. Transgenic mice susceptible to poliovirus. Proc Natl Acad Sci U S A. 1991 Feb 1;88(3):951–955. doi: 10.1073/pnas.88.3.951. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Kuge S., Nomoto A. Construction of viable deletion and insertion mutants of the Sabin strain of type 1 poliovirus: function of the 5' noncoding sequence in viral replication. J Virol. 1987 May;61(5):1478–1487. doi: 10.1128/jvi.61.5.1478-1487.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. 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]
  13. 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]
  14. 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]
  15. Macadam A. J., Pollard S. R., Ferguson G., Skuce R., Wood D., Almond J. W., Minor P. D. Genetic basis of attenuation of the Sabin type 2 vaccine strain of poliovirus in primates. Virology. 1993 Jan;192(1):18–26. doi: 10.1006/viro.1993.1003. [DOI] [PubMed] [Google Scholar]
  16. Martin A., Benichou D., Couderc T., Hogle J. M., Wychowski C., Van der Werf S., Girard M. Use of type 1/type 2 chimeric polioviruses to study determinants of poliovirus type 1 neurovirulence in a mouse model. Virology. 1991 Feb;180(2):648–658. doi: 10.1016/0042-6822(91)90078-p. [DOI] [PubMed] [Google Scholar]
  17. Mendelsohn C. L., Wimmer E., Racaniello V. R. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell. 1989 Mar 10;56(5):855–865. doi: 10.1016/0092-8674(89)90690-9. [DOI] [PubMed] [Google Scholar]
  18. Nomoto A., Omata T., Toyoda H., Kuge S., Horie H., Kataoka Y., Genba Y., Nakano Y., Imura N. Complete nucleotide sequence of the attenuated poliovirus Sabin 1 strain genome. Proc Natl Acad Sci U S A. 1982 Oct;79(19):5793–5797. doi: 10.1073/pnas.79.19.5793. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Omata T., Kohara M., Kuge S., Komatsu T., Abe S., Semler B. L., Kameda A., Itoh H., Arita M., Wimmer E. Genetic analysis of the attenuation phenotype of poliovirus type 1. J Virol. 1986 May;58(2):348–358. doi: 10.1128/jvi.58.2.348-358.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. PIZZI M. Sampling variation of the fifty percent end-point, determined by the Reed-Muench (Behrens) method. Hum Biol. 1950 Sep;22(3):151–190. [PubMed] [Google Scholar]
  21. Pilipenko E. V., Blinov V. M., Romanova L. I., Sinyakov A. N., Maslova S. V., Agol V. I. Conserved structural domains in the 5'-untranslated region of picornaviral genomes: an analysis of the segment controlling translation and neurovirulence. Virology. 1989 Feb;168(2):201–209. doi: 10.1016/0042-6822(89)90259-6. [DOI] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Ren R. B., Costantini F., Gorgacz E. J., Lee J. J., Racaniello V. R. Transgenic mice expressing a human poliovirus receptor: a new model for poliomyelitis. Cell. 1990 Oct 19;63(2):353–362. doi: 10.1016/0092-8674(90)90168-e. [DOI] [PubMed] [Google Scholar]
  25. 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]
  26. Ren R., Racaniello V. R. Human poliovirus receptor gene expression and poliovirus tissue tropism in transgenic mice. J Virol. 1992 Jan;66(1):296–304. doi: 10.1128/jvi.66.1.296-304.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. 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]
  29. 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]
  30. 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]
  31. 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]
  32. 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]

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