Chapter 21 : Poliomyelitis

MyBook is a cheap paperback edition of the original book and will be sold at uniform, low price.

Preview this chapter:
Zoom in

Poliomyelitis, Page 1 of 2

| /docserver/preview/fulltext/10.1128/9781555816698/9781555816032_Chap21-1.gif /docserver/preview/fulltext/10.1128/9781555816698/9781555816032_Chap21-2.gif


Poliovirus (PV) is the causative agent of poliomyelitis, an acute human disease of the central nervous system (CNS). This chapter provides a review of recent advances in our understanding of PV pathogenicity. The host range of most PV strains is restricted to primates, with humans as the natural host. The PV receptor (PVR) was identified by taking advantage of the species-specific nature of infection. Mouse cells are not susceptible to PV infection but permit PV replication when PV RNA is transfected, circumventing infection through the cell surface. The infected mice exhibit clinical signs and pathological lesions that resemble human poliomyelitis after intracerebral, intraperitoneal, intravenous, intramuscular, or intranasal inoculation of PV. In addition to monkeys, PVR-Tg21 mice are recognized by the World Health Organization as an animal model of poliomyelitis. Provocation poliomyelitis was experimentally reproduced in transgenic (tg) mice, with results that suggested that skeletal muscle injury stimulates retrograde axonal transport of PV and thereby facilitates viral invasion of the CNS, with resultant spinal cord damage. The quasispecies of PV plays an important role in PV pathogenesis. PV, as well as other RNA viruses, has a high error rate in RNA replication, and therefore each viral genome in the population differs from others by one or more mutations.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
Highlighted Text: Show | Hide
Loading full text...

Full text loading...


Image of Figure 1.
Figure 1.

Scheme of PV pathogenesis and possible barriers that prevent PV dissemination. There are several host barriers that block the progression of PV dissemination. The host range of PV is restricted to simians, so other animal species are not susceptible to PV infection (host range barrier). In humans, after PV is ingested, PV initially replicates in the oropharyngeal and intestinal mucosa and enters the host despite a physical barrier at the GI mucosa (GI tract barriers). When PV reaches the blood, PV replicates poorly in the extraneural tissues, suggesting the presence of a barrier that prevents efficient replication of PV in these tissues. The CNS is physically isolated from the extraneural tissues by the blood-brain barrier (BBB), which acts as a physical barrier preventing free movement of substances between the bloodstream and the parenchyma of the CNS. PV permeates this barrier by an unknown mechanism. PV also reaches the CNS via retrograde axonal transport, a pathway for PV that is dependent on the PVR. PV finally replicates in neurons in the CNS. The replication sites in the CNS are restricted to certain neurons, suggesting the presence of unknown barriers in nonsusceptible neurons. Replication of attenuated PV strains is strongly suppressed in neurons, suggesting PV strain-specific barriers in the CNS.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 2.
Figure 2.

Structure of the GI tract barrier. The epithelial cells (enterocytes) lining the GI tract form a tight physical barrier for PV infection. A structure called FAE is present in Peyer’s patches above the lymphoid follicle and contains M cells, which are capable of transporting molecules from the intestinal lumen into the underlying dendritic cells or macrophages. The primary replication sites of PV and the source of excreted virus have not yet been determined. It is also unknown whether PV replicates in the epithelial cells in a PVR-dependent manner or whether PV is incorporated via M cells by transcytosis without lytic infection.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 3.
Figure 3.

Innate immune barrier in extraneural tissues. Although many tissues are exposed to PV during the viremic phase, PV replication in the extraneural tissues is strongly suppressed by the innate immune response, which is mediated by type I IFN. Many cells in the extraneural tissues possess all of the host factors required for PV replication and have the potential to support PV replication. Soon after infection of a single cell, an active host innate immune defense induces an antiviral state in the surrounding cells and stops the cascade of viral infection in these sites. Thus, this response acts as an immunological barrier. In neural tissues, however, the innate immune response is less active than in the extraneural tissues, allowing a sequential cascade of viral infection.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint
Image of Figure 4.
Figure 4.

Two pathways of CNS invasion. PV is able to enter the CNS by at least two distinct pathways. One pathway involves the direct penetration of the BBB from the bloodstream into the parenchyma of the CNS. The BBB is composed of endothelial cells of blood vessels that are sealed together at their edges by tight junctions. Generally, it does not allow free transport of pathogens. There is no strong evidence that supports direct infection of endothelial cells. Physiological pharmacokinetic analysis suggests that the PV is able to permeate the BBB from the bloodstream into the parenchyma of the CNS independently of PVR. The precise mechanism by which PV employs this pathway remains to be elucidated. Another pathway leading to neural dissemination of PV is by retrograde axonal transport. PV is incorporated into endosomes by PVR-mediated endocytosis at neuromuscular junctions. The C-terminal cytoplasmic tail of the PVR on the surface of the endosome is able to bind TCTEL1 (in humans) or Tctex-1(in mice), which is the light chain-1 of the cytoplasmic dynein complex. PV-containing endosomes move on the microtubules along the axon via retrograde transport at a rate of more than 12 cm/day, a velocity classified as fast retrograde axonal transport. PV particles do not initiate conformational changes during transport along the axon until they reach the cell body of the neuron.

Citation: Koike S, Nomoto A. 2010. Poliomyelitis, p 339-351. In Ehrenfeld E, Domingo E, Roos R (ed), The Picornaviruses. ASM Press, Washington, DC. doi: 10.1128/9781555816698.ch21
Permissions and Reprints Request Permissions
Download as Powerpoint


1. Aoki, J.,, S. Koike,, I. Ise,, Y. Sato-Yoshida, and, A. Nomoto. 1994. Amino acid residues on human poliovirus receptor involved in interaction with poliovirus. J Biol. Chem. 269: 84318438.
2. Armstrong, C. 1939. Successful transfer of Lansing strain of poliomyelitis virus from the cotton rat to the white mouse. Public Health Rep. 54: 23032305.
3. Belnap, D. M.,, B. M. McDermott, Jr.,, D. J. Filman,, N. Cheng,, B. L. Trus,, H. J. Zuccola,, V. R. Racaniello,, J. M. Hogle, and, A. C. Steven. 2000. Three-dimensional structure of poliovirus receptor bound to poliovirus. Proc. Natl. Acad. Sci. USA 97: 7378.
4. Bernhardt, G.,, J. Harber,, A. Zibert,, M. deCrombrugghe, and, E. Wimmer. 1994. The poliovirus receptor: identification of domains and amino acid residues critical for virus binding. Virology 203: 344356.
5. Blyn, L. B.,, K. M. Swiderek,, O. Richards,, D. C. Stahl,, B. L. Semler, and, E. Ehrenfeld. 1996. Poly(rC) binding protein 2 binds to stem-loop IV of the poliovirus RNA 5′ noncoding region: identification by automated liquid chromatography-tandem mass spectrometry. Proc. Natl. Acad. Sci. USA 93: 1111511120.
6. Bodian, D. 1955. Emerging concept of poliomyelitis infection. Science 122: 105108.
7. Bodian, D. 1949. Histopathologic basis of clinical findings in poliomyelitis. Am. J. Med. 6: 563578.
8. Bodian, D. 1959. Poliomyelitis: pathogenesis and histopathology, p. 479–518. In T. M. Rivers and, F. L. Horsfall, Jr. (ed.), Viral and Rickettsial Infections of Man, vol. 3. J. B. Lippincott, Philadelphia, PA.
9. Bodian, D. 1956. Poliovirus in chimpanzee tissues after virus feeding. Am. J. Hyg. 64: 181197.
10. Bodian, D. 1954. Viremia in experimental poliomyelitis. II. Viremia and the mechanism of the provoking effect of injections or trauma. Am. J. Hyg. 60: 358370.
11. Bodian, D., and, A. Howe. 1940. An experimental study of the role of neurons in the dissemination of poliomyelitis virus in the nervous system. Brain 63: 135162.
12. Brady, S. T. 1991. Molecular motors in the nervous system. Neuron 7: 521533.
13. Couderc, T.,, T. Barzu,, F. Horaud, and, R. Crainic. 1990. Poliovirus permissivity and specific receptor expression on human endothelial cells. Virology 174: 95102.
14. Coyne, C. B.,, K. S. Kim, and, J. M. Bergelson. 2007. Poliovirus entry into human brain microvascular cells requires receptor-induced activation of SHP-2. EMBO J. 26: 40164028.
15. Crotty, S.,, L. Hix,, L. J. Sigal, and, R. Andino. 2002. Poliovirus pathogenesis in a new poliovirus receptor transgenic mouse model: age-dependent paralysis and a mucosal route of infection. J. Gen. Virol. 83: 17071720.
16. del Angel, R. M.,, A. G. Papavassiliou,, C. Fernandez-Tomas,, S. J. Silverstein, and, V. R. Racaniello. 1989. Cell proteins bind to multiple sites within the 5′ untranslated region of poliovirus RNA. Proc. Natl. Acad. Sci. USA 86: 82998303.
17. Domingo, E., and, J. J. Holland. 1997. RNA virus mutations and fitness for survival. Annu. Rev. Microbiol. 51: 151178.
18. Domingo, E.,, L. Menendez-Arias, and, J. J. Holland. 1997. RNA virus fitness. Rev. Med. Virol. 7: 8796.
19. Dragunsky, E.,, T. Nomura,, K. Karpinski,, J. Furesz,, D. J. Wood,, Y. Pervikov,, S. Abe,, T. Kurata,, O. Vanloocke,, G. Karganova,, R. Taffs,, A. Heath,, A. Ivshina, and, I. Levenbook. 2003. Transgenic mice as an alternative to monkeys for neurovirulence testing of live oral poliovirus vaccine: validation by a WHO collaborative study. Bull. W. H. O. 81: 251260.
20. Enders, J. F.,, T. H. Weller, and, F. C. Robbins. 1949. Cultivation of the Lansing strain of poliomyelitis virus in cultures of various human embryonic tissues. Science 109: 8587.
21. Evans, D. M.,, G. Dunn,, P. D. Minor,, G. C. Schild,, A. J. Cann,, G. Stanway,, J. W. Almond,, K. Currey, and, J. V. Maizel, Jr. 1985. Increased neurovirulence associated with a single nucleotide change in a noncoding region of the Sabin type 3 poliovaccine genome. Nature 314: 548550.
22. Freistadt, M. S.,, G. Kaplan, and, V. R. Racaniello. 1990. Heterogeneous expression of poliovirus receptor-related proteins in human cells and tissues. Mol. Cell. Biol. 10: 57005706.
23. Freistadt, M. S., and, V. R. Racaniello. 1991. Mutational analysis of the cellular receptor for poliovirus. J. Virol. 65: 38733876.
24. Garcia-Sastre, A.,, R. K. Durbin,, H. Zheng,, P. Palese,, R. Gertner,, D. E. Levy, and, J. E. Durbin. 1998. The role of interferon in influenza virus tissue tropism. J. Virol. 72: 85508558.
25. Goldstein, G. W., and, A. L. Betz. 1986. The blood-brain barrier. Sci. Am. 255: 7483.
26. Gosert, R.,, K. H. Chang,, R. Rijnbrand,, M. Yi,, D. V. Sangar, and, S. M. Lemon. 2000. Transient expression of cellular polypyrimidine-tract binding protein stimulates cap-independent translation directed by both picornaviral and flaviviral internal ribosome entry sites in vivo. Mol. Cell. Biol. 20: 15831595.
27. Gromeier, M.,, L. Alexander, and, E. Wimmer. 1996. Internal ribosomal entry site substitution eliminates neurovirulence in intergeneric poliovirus recombinants. Proc. Natl. Acad. Sci. USA 93: 23702375.
28. Gromeier, M., and, E. Wimmer. 1998. Mechanism of injury-provoked poliomyelitis. J. Virol. 72: 50565060.
29. Guest, S.,, E. Pilipenko,, K. Sharma,, K. Chumakov, and, R. P. Roos. 2004. Molecular mechanisms of attenuation of the Sabin strain of poliovirus type 3. J. Virol. 78: 1109711107.
30. Gutierrez, A. L.,, M. Denova-Ocampo,, V. R. Racaniello, and, R. M. del Angel. 1997. Attenuating mutations in the polio-virus 5′ untranslated region alter its interaction with polypyrimidine tract-binding protein. J. Virol. 71: 38263833.
31. Haller, A. A.,, J. H. Nguyen, and, B. L. Semler. 1993. Minimum internal ribosome entry site required for poliovirus infectivity. J. Virol. 67: 74617471.
32. Haller, A. A.,, S. R. Stewart, and, B. L. Semler. 1996. Attenuation stem-loop lesions in the 5′ noncoding region of poliovirus RNA: neuronal cell-specific translation defects. J. Virol. 70: 14671474.
33. He, Y.,, V. D. Bowman,, S. Mueller,, C. M. Bator,, J. Bella,, X. Peng,, T. S. Baker,, E. Wimmer,, R. J. Kuhn, and, M. G. Rossmann. 2000. Interaction of the poliovirus receptor with poliovirus. Proc. Natl. Acad. Sci. USA 97: 7984.
34. Hellen, C. U.,, T. V. Pestova,, M. Litterst, and, E. Wimmer. 1994. The cellular polypeptide p57 (pyrimidine tract-binding protein) binds to multiple sites in the poliovirus 5′ nontranslated region. J. Virol. 68: 941950.
35. Hellen, C. U.,, G. W. Witherell,, M. Schmid,, S. H. Shin,, T. V. Pestova,, A. Gil, and, E. Wimmer. 1993. A cytoplasmic 57-kDa protein that is required for translation of picornavirus RNA by internal ribosomal entry is identical to the nuclear pyrimidine tract-binding protein. Proc. Natl. Acad. Sci. USA 90: 76427646.
36. Holland, J. J. 1961. Receptor affinities as major determinants of enterovirus tissue tropisms in humans. Virology 15: 312326.
37. Holland, J. J.,, L. McLaren, and, J. T. Syverton. 1959. Mammalian cell-virus relationship. III. Poliovirus production by non-primate cells exposed to poliovirus ribonucleic acid. Proc. Soc. Exp. Biol. Med. 100: 843845.
38. Holland, J. J.,, L. McLaren, and, J. T. Syverton. 1959. The mammalian cell-virus relationship. IV. Infection of naturally insusceptible cells with enterovirus ribonucleic acid. J. Exp. Med. 110: 6580.
39. Horstmann, D. M.,, J. L. Melnick,, R. Ward, and, J. S. Fleitas. 1947. The susceptibility of infant rhesus monkeys to poliomyelitis virus administered by mouth A study of the distribution of virus in the tissues of orally infected animals. J. Exp. Med. 86: 309323.
40. Hsiung, G.-D.,, F. L. Black, and, J. R. Henderson. 1964. Susceptibility of primates to viruses in relation to taxonomic classification, p. 1–23. In J. Buettner-Jaenusch (ed.), Evolutionary and Genetic Biology of Primates, vol. 2. Academic Press, New York, NY.
41. Hunt, S. L.,, J. J. Hsuan,, N. Totty, and, R. J. Jackson. 1999. unr, a cellular cytoplasmic RNA-binding protein with five cold-shock domains, is required for internal initiation of translation of human rhinovirus RNA. Genes Dev. 13: 437448.
42. Hunt, S. L., and, R. J. Jackson. 1999. Polypyrimidine-tract binding protein (PTB) is necessary, but not sufficient, for efficient internal initiation of translation of human rhinovirus-2 RNA. RNA 5: 344359.
43. Ida-Hosonuma, M.,, T. Iwasaki,, C. Taya,, Y. Sato,, J. Li,, N. Nagata,, H. Yonekawa, and, S. Koike. 2002. Comparison of neuropathogenicity of poliovirus in two transgenic mouse strains expressing human poliovirus receptor with different distribution patterns. J. Gen. Virol. 83: 10951105.
44. Ida-Hosonuma, M.,, T. Iwasaki,, T. Yoshikawa,, N. Nagata,, Y. Sato,, T. Sata,, M. Yoneyama,, T. Fujita,, C. Taya,, H. Yonekawa, and, S. Koike. 2005. The alpha/beta interferon response controls tissue tropism and pathogenicity of poliovirus. J. Virol. 79: 44604469.
45. Ida-Hosonuma, M.,, Y. Sasaki,, H. Toyoda,, A. Nomoto,, O. Gotoh,, H. Yonekawa, and, S. Koike. 2003. Host range of poliovirus is restricted to simians because of a rapid sequence change of the poliovirus receptor gene during evolution. Arch. Virol. 148: 2944.
46. Iwasaki, A.,, R. Welker,, S. Mueller,, M. Linehan,, A. Nomoto, and, E. Wimmer. 2002. Immunofluorescence analysis of poliovirus receptor expression in Peyer’s patches of humans, primates, and CD155 transgenic mice: implications for poliovirus infection. J. Infect. Dis. 186: 585592.
47. Kanamitsu, M.,, A. Kasamaki,, M. Ogawa,, S. Kasahara, and, M. Imamura. 1967. Immunofluorescent study on the pathogenesis of oral infection of poliovirus in monkeys. Jpn. J. Med. Sci. Biol. 20: 175194.
48. Kauder, S. E., and, V. R. Racaniello. 2004. Poliovirus tropism and attenuation are determined after internal ribosome entry. J. Clin. Investig. 113: 17431753.
49. Kawamura, N.,, M. Kohara,, S. Abe,, T. Komatsu,, K. Tago,, M. Arita, and, A. Nomoto. 1989. Determinants in the 5′ noncoding region of poliovirus Sabin 1 RNA that influence the attenuation phenotype. J. Virol. 63: 13021309.
50. Khan, S.,, X. Peng,, J. Yin,, P. Zhang, and, E. Wimmer. 2008. Characterization of the New World monkey homologues of human poliovirus receptor CD155. J. Virol. 82: 71677179.
51. Kikuchi, T.,, M. Ichikawa,, J. Arai,, H. Tateiwa,, L. Fu,, K. Higuchi, and, N. Yoshimura. 2000. Molecular cloning and characterization of a new neuron-specific homologue of rat polypyrimidine tract binding protein. J. Biochem. 128: 811821.
52. Koike, S.,, J. Aoki, and, A. Nomoto. 1994. Transgenic mouse model for the study of poliovirus pathogenesis, p. 463–480. In E. Wimmer and, R. Weiss (ed.), Receptor-Mediated Virus Entry into Cells. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
53. Koike, S.,, H. Horie,, I. Ise,, A. Okitsu,, M. Yoshida,, N. Iizuka,, K. Takeuchi,, T. Takegami, and, A. Nomoto. 1990. The poliovirus receptor protein is produced both as membrane-bound and secreted forms. EMBO J. 9: 32173224.
54. Koike, S.,, I. Ise, and, A. Nomoto. 1991. Functional domains of the poliovirus receptor. Proc. Natl. Acad. Sci. USA 88: 41044108.
55. Koike, S.,, I. Ise,, Y. Sato,, H. Yonekawa,, O. Gotoh, and, A. Nomoto. 1992. A second gene for the African green monkey poliovirus receptor that has no putative N-glycosylation site in the functional N-terminal immunoglobulin-like domain. J. Virol. 66: 70597066.
56. Koike, S.,, C. Taya,, J. Aoki,, Y. Matsuda,, I. Ise,, H. Takeda,, T. Matsuzaki,, H. Amanuma,, H. Yonekawa, and, A. Nomoto. 1994. Characterization of three different transgenic mouse lines that carry human poliovirus receptor gene: influence of the transgene expression on pathogenesis. Arch. Virol. 139: 351363.
57. Koike, S.,, C. Taya,, T. Kurata,, S. Abe,, I. Ise,, H. Yonekawa, and, A. Nomoto. 1991. Transgenic mice susceptible to poliovirus. Proc. Natl. Acad. Sci. USA 88: 951955.
58. Kunin, C. M., and, W. S. Jordan, Jr. 1961. In vitro absorption of poliovirus by noncultured tissues. Effect of species, age and malignancy. Am. J. Hyg. 73: 245257.
59. Kuss, S. K.,, C. A. Etheredge, and, J. K. Pfeiffer. 2008. Multiple host barriers restrict poliovirus trafficking in mice. PLoS Pathog. 4: e1000082.
60. La Monica, N.,, J. W. Almond, and, V. R. Racaniello. 1987. A mouse model for poliovirus neurovirulence identifies mutations that attenuate the virus for humans. J. Virol. 61: 29172920.
61. La Monica, N., and, V. R. Racaniello. 1989. Differences in replication of attenuated and neurovirulent polioviruses in human neuroblastoma cell line SH-SY5Y. J. Virol. 63: 23572360.
62. Landsteiner, K., and, E. Popper. 1908. Microscopische präparate von einem menschlichen und zwei affentückermarker. Wein. Klin. Wochenschr. 21: 1930.
63. Lillevali, K.,, A. Kulla, and, T. Ord. 2001. Comparative expression analysis of the genes encoding polypyrimidine tract binding protein (PTB) and its neural homologue (brPTB) in prenatal and postnatal mouse brain. Mech. Dev. 101: 217220.
64. Macadam, A. J.,, S. R. Pollard,, G. Ferguson,, G. Dunn,, R. Skuce,, J. W. Almond, and, P. D. Minor. 1991. The 5′ noncoding region of the type 2 poliovirus vaccine strain contains determinants of attenuation and temperature sensitivity. Virology 181: 451458.
65. Markovtsov, V.,, J. M. Nikolic,, J. A. Goldman,, C. W. Turck,, M. Y. Chou, and, D. L. Black. 2000. Cooperative assembly of an hnRNP complex induced by a tissue-specific homolog of polypyrimidine tract binding protein. Mol. Cell. Biol. 20: 74637479.
66. Meerovitch, K.,, J. Pelletier, and, N. Sonenberg. 1989. A cellular protein that binds to the 5′-noncoding region of poliovirus RNA: implications for internal translation initiation. Genes Dev. 3: 10261034.
67. Mendelsohn, C.,, B. Johnson,, K. A. Lionetti,, P. Nobis,, E. Wimmer, and, V. R. Racaniello. 1986. Transformation of a human poliovirus receptor gene into mouse cells. Proc. Natl. Acad. Sci. USA 83: 78457849.
68. Mendelsohn, C. L.,, E. Wimmer, and, V. R. Racaniello. 1989. Cellular receptor for poliovirus: molecular cloning, nucleotide sequence, and expression of a new member of the immunoglobulin superfamily. Cell 56: 855865.
69. Miller, D. A.,, O. J. Miller,, V. G. Dev,, S. Hashmi,, R. Tantravahi,, L. Medrano, and, H. Green. 1974. Human chromosome 19 carries a poliovirus receptor gene. Cell 1: 161173.
70. Morrison, M. E.,, Y. J. He,, M. W. Wien,, J. M. Hogle, and, V. R. Racaniello. 1994. Homolog-scanning mutagenesis reveals poliovirus receptor residues important for virus binding and replication. J. Virol. 68: 25782588.
71. Mrkic, B.,, J. Pavlovic,, T. Rulicke,, P. Volpe,, C. J. Buchholz,, D. Hourcade,, J. P. Atkinson,, A. Aguzzi, and, R. Cattaneo. 1998. Measles virus spread and pathogenesis in genetically modified mice. J. Virol. 72: 74207427.
72. Mueller, S.,, X. Cao,, R. Welker, and, E. Wimmer. 2002. Interaction of the poliovirus receptor CD155 with the dynein light chain T ctex-1 and its implication for poliovirus pathogenesis. J. Biol. Chem. 277: 78977904.
73. Mueller, S.,, E. Wimmer, and, J. Cello. 2005. Poliovirus and poliomyelitis: a tale of guts, brains, and an accidental event. Virus Res. 111: 175193.
74. Muller, U.,, U. Steinhoff,, L. F. Reis,, S. Hemmi,, J. Pavlovic,, R. M. Zinkernagel, and, M. Aguet. 1994. Functional role of type I and type II interferons in antiviral defense. Science 264: 19181921.
75. Nagata, N.,, T. Iwasaki,, Y. Ami,, Y. Sato,, I. Hatano,, A. Harashima,, Y. Suzaki,, T. Yoshii,, T. Hashikawa,, T. Sata,, Y. Horiuchi,, S. Koike,, T. Kurata, and, A. Nomoto. 2004. A poliomyelitis model through mucosal infection in transgenic mice bearing human poliovirus receptor, TgPVR21. Virology 321: 87100.
76. Nathanson, N. 2008. The pathogenesis of poliomyelitis: what we don’t know. Adv. Virus Res. 71: 150.
77. Nathanson, N., and, D. Bodian. 1961. Experimental poliomyelitis following intramuscular virus injection. I. The effect of neural block on a neurotropic and a pantropic strain. Bull. Johns Hopkins Hosp. 108: 308319.
78. Nathanson, N., and, A. D. Langmuir. 1963. The Cutter incident. Poliomyelitis following formaldehyde-inactivated poliovirus vaccination in the United States during the spring of 1955. II. Relationship of poliomyelitis to Cutter vaccine. Am. J. Hyg. 78: 2960.
79. Neutra, M. R.,, E. Pringault, and, J. P. Kraehenbuhl. 1996. Antigen sampling across epithelial barriers and induction of mucosal immune responses. Annu. Rev. Immunol. 14: 275300.
80. Nobis, P.,, R. Zibirre,, G. Meyer,, J. Kuhne,, G. Warnecke, and, G. Koch. 1985. Production of a monoclonal antibody against an epitope on HeLa cells that is the functional poliovirus binding site. J. Gen. Virol. 66: 25632569.
81. Ochs, K.,, L. Saleh,, G. Bassili,, V. H. Sonntag,, A. Zeller, and, M. Niepmann. 2002. Interaction of translation initiation factor eIF4B with the poliovirus internal ribosome entry site. J. Virol. 76: 21132122.
82. Ochs, K.,, A. Zeller,, L. Saleh,, G. Bassili,, Y. Song,, A. Sonntag, and, M. Niepmann. 2003. Impaired binding of standard initiation factors mediates poliovirus translation attenuation. J. Virol. 77: 115122.
83. Ohka, S.,, H. Igarashi,, N. Nagata,, M. Sakai,, S. Koike,, T. Nochi,, H. Kiyono, and, A. Nomoto. 2007. Establishment of a poliovirus oral infection system in human poliovirus receptor-expressing transgenic mice that are deficient in alpha/beta interferon receptor. J. Virol. 81: 79027912.
84. Ohka, S.,, N. Matsuda,, K. Tohyama,, T. Oda,, M. Morikawa,, S. Kuge, and, A. Nomoto. 2004. Receptor (CD155)-dependent endocytosis of poliovirus and retrograde axonal transport of the endosome. J. Virol. 78: 71867198.
85. Ohka, S., and, A. Nomoto. 2001. Recent insights into poliovirus pathogenesis. Trends Microbiol. 9: 501506.
86. Ohka, S.,, M. Sakai,, S. Bohnert,, H. Igarashi,, K. Deinhardt,, G. Schiavo, and, A. Nomoto. 2009. Receptor-dependent and -independent axonal retrograde transport of poliovirus in motor neurons. J. Virol. 83: 49955004.
87. Ohka, S.,, W. X. Yang,, E. Terada,, K. Iwasaki, and, A. Nomoto. 1998. Retrograde transport of intact poliovirus through the axon via the fast transport system. Virology 250: 6775.
88. Omata, T.,, M. Kohara,, S. Kuge,, T. Komatsu,, S. Abe,, B. L. Semler,, A. Kameda,, H. Itoh,, M. Arita,, E. Wimmer, et al. 1986. Genetic analysis of the attenuation phenotype of poliovirus type 1. J. Virol. 58: 348358.
89. Ouzilou, L.,, E. Caliot,, I. Pelletier,, M. C. Prevost,, E. Pringault, and, F. Colbere-Garapin. 2002. Poliovirus transcytosis through M-like cells. J. Gen. Virol. 83: 21772182.
90. Owen, R. L., and, A. L. Jones. 1974. Epithelial cell specialization within human Peyer’s patches: an ultrastructural study of intestinal lymphoid follicles. Gastroenterology 66: 189203.
91. Pelletier, J., and, N. Sonenberg. 1988. Internal initiation of translation of eukaryotic mRNA directed by a sequence derived from poliovirus RNA. Nature 334: 320325.
92. Pestova, T. V.,, C. U. Hellen, and, E. Wimmer. 1991. Translation of poliovirus RNA: role of an essential cis-acting oligopyrimidine element within the 5′ nontranslated region and involvement of a cellular 57-kilodalton protein. J. Virol. 65: 61946204.
93. Pfeiffer, J. K., and, K. Kirkegaard. 2003. A single mutation in poliovirus RNA-dependent RNA polymerase confers resistance to mutagenic nucleotide analogs via increased fidelity. Proc. Natl. Acad. Sci. USA 100: 72897294.
94. Pfeiffer, J. K., and, K. Kirkegaard. 2006. Bottleneck-mediated quasispecies restriction during spread of an RNA virus from inoculation site to brain. Proc. Natl. Acad. Sci. USA 103: 55205525.
95. Pfeiffer, J. K., and, K. Kirkegaard. 2005. Increased fidelity reduces poliovirus fitness and virulence under selective pressure in mice. PLoS Pathog. 1: e11.
96. Pilipenko, E. V.,, T. V. Pestova,, V. G. Kolupaeva,, E. V. Khitrina,, A. N. Poperechnaya,, V. I. Agol, and, C. U. Hellen. 2000. A cell cycle-dependent protein serves as a template-specific translation initiation factor. Genes Dev. 14: 20282045.
97. Pilipenko, E. V.,, E. G. Viktorova,, E. V. Khitrina,, S. V. Maslova,, N. Jarousse,, M. Brahic, and, V. I. Agol. 1999. Distinct attenuation phenotypes caused by mutations in the translational starting window of Theiler’s murine encephalomyelitis virus. J. Virol. 73: 31903196.
98. Polydorides, A. D.,, H. J. Okano,, Y. Y. Yang,, G. Stefani, and, R. B. Darnell. 2000. A brain-enriched polypyrimidine tract-binding protein antagonizes the ability of Nova to regulate neuron-specific alternative splicing. Proc. Natl. Acad. Sci. USA 97: 63506355.
99. Racaniello, V. R. 2006. One hundred years of poliovirus pathogenesis. Virology 344: 916.
100. Ren, R., and, V. R. Racaniello. 1992. Human poliovirus receptor gene expression and poliovirus tissue tropism in transgenic mice. J. Virol. 66: 296304.
101. Ren, R., and, V. R. Racaniello. 1992. Poliovirus spreads from muscle to the central nervous system by neural pathways. J. Infect. Dis. 166: 747752.
102. Ren, R. B.,, F. Costantini,, E. J. Gorgacz,, J. J. Lee, and, V. R. Racaniello. 1990. Transgenic mice expressing a human poliovirus receptor: a new model for poliomyelitis. Cell 63: 353362.
103. Ryman, K. D.,, W. B. Klimstra,, K. B. Nguyen,, C. A. Biron, and, R. E. Johnston. 2000. Alpha/beta interferon protects adult mice from fatal Sindbis virus infection and is an important determinant of cell and tissue tropism. J. Virol. 74: 33663378.
104. Sabin, A., and, L. Boulger. 1973. History of Sabin attenuated poliovirus oral live vaccine strains. J. Biol. Stand. 1: 115118.
105. Sabin, A. B. 1965. Oral poliovirus vaccine. History of its development and prospects for eradication of poliomyelitis. JAMA 194: 872876.
106. Sabin, A. B. 1956. Pathogenesis of poliomyelitis; reappraisal in the light of new data. Science 123: 11511157.
107. Salk, J. E. 1953. Principles of immunization as applied to poliomyelitis and influenza. Am. J. Public Health Nations Health 43: 13841398.
108. Selinka, H. C.,, A. Zibert, and, E. Wimmer. 1991. Poliovirus can enter and infect mammalian cells by way of an intercellular adhesion molecule 1 pathway. Proc. Natl. Acad. Sci. USA 88: 35983602.
109. Sicinski, P.,, J. Rowinski,, J. B. Warchol,, Z. Jarzabek,, W. Gut,, B. Szczygiel,, K. Bielecki, and, G. Koch. 1990. Poliovirus type 1 enters the human host through intestinal M cells. Gastroenterology 98: 5658.
110. Takahashi, Y.,, S. Misumi,, A. Muneoka,, M. Masuyama,, H. Tokado,, K. Fukuzaki,, N. Takamune, and, S. Shoji. 2008. Nonhuman primate intestinal villous M-like cells: an effective poliovirus entry site. Biochem. Biophys. Res. Commun. 368: 501507.
111. Vignuzzi, M.,, J. K. Stone,, J. J. Arnold,, C. E. Cameron, and, R. Andino. 2006. Quasispecies diversity determines pathogenesis through cooperative interactions in a viral population. Nature 439: 344348.
112. Wenner, H. A.,, P. Kamitsuka,, M. Lenahan, and, I. Archetti. 1960. The pathogenesis of poliomyelitis. Sites of multiplication of poliovirus in cynomolgus monkeys after alimentary infection. Arch. Gesamte Virusforsch. 9: 537558.
113. Wessely, R.,, K. Klingel,, K. U. Knowlton, and, R. Kandolf. 2001. Cardioselective infection with coxsackievirus B3 requires intact type I interferon signaling: implications for mortality and early viral replication. Circulation 103: 756761.
114. Westrop, G. D.,, K. A. Wareham,, D. M. Evans,, G. Dunn,, P. D. Minor,, D. I. Magrath,, F. Taffs,, S. Marsden,, M. A. Skinner,, G. C. Schild, et al. 1989. Genetic basis of attenuation of the Sabin type 3 oral poliovirus vaccine. J. Virol. 63: 13381344.
115. Yanagiya, A.,, S. Ohka,, N. Hashida,, M. Okamura,, C. Taya,, N. Kamoshita,, K. Iwasaki,, Y. Sasaki,, H. Yonekawa, and, A. Nomoto. 2003. Tissue-specific replicating capacity of a chimeric poliovirus that carries the internal ribosome entry site of hepatitis C virus in a new mouse model transgenic for the human poliovirus receptor. J. Virol. 77: 1047910487.
116. Yang, W. X.,, T. Terasaki,, K. Shiroki,, S. Ohka,, J. Aoki,, S. Tanabe,, T. Nomura,, E. Terada,, Y. Sugiyama, and, A. Nomoto. 1997. Efficient delivery of circulating poliovirus to the central nervous system independently of poliovirus receptor. Virology 229: 421428.
117. Yoshikawa, T.,, T. Iwasaki,, M. Ida-Hosonuma,, M. Yoneyama,, T. Fujita,, H. Horie,, M. Miyazawa,, S. Abe,, B. Simizu, and, S. Koike. 2006. Role of the alpha/beta interferon response in the acquisition of susceptibility to poliovirus by kidney cells in culture. J. Virol. 80: 43134325.
118. Zhang, S., and, V. R. Racaniello. 1997. Expression of the poliovirus receptor in intestinal epithelial cells is not sufficient to permit poliovirus replication in the mouse gut. J. Virol. 71: 49154920.

This is a required field
Please enter a valid email address
Please check the format of the address you have entered.
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error