Skip to main content
PMC home page
Journal of Virology logoLink to Journal of Virology
. 1996 Sep;70(9):6395–6401. doi: 10.1128/jvi.70.9.6395-6401.1996

Persistent poliovirus infection of human fetal brain cells.

N Pavio 1, M H Buc-Caron 1, F Colbère-Garapin 1
PMCID: PMC190667  PMID: 8709269

Abstract

It has been suggested that poliovirus (PV), the causative agent of poliomyelitis, could persist in surviving patients. We have previously shown that PV can persistently infect some human cell lines in vitro, particularly neuroblastoma cell lines. We report here an ex vivo model in which PV can persistently infect primary cultures of human fetal brain cells. Two mutations involving capsid residues 142 of VP2 and 95 of VP1 were repeatedly selected during the persistent infections. These residues are located in capsid regions known to be involved in interactions between PV and its receptor. During the first week after infection, viral antigens were found in cells of both the neuronal and glial lineages. In contrast, 2 weeks after infection, viral antigens were detected almost exclusively in cells of the neuronal lineage. They were detected predominantly in cells expressing a marker of early commitment to the neuronal lineage, MAP-5, particularly in neuroblasts. Viral antigens were also found in immature progenitors expressing a neuroepithelium marker, nestin, and in cells expressing a marker of postmitotic neurons, MAP-2. The presence of viral antigens in postmitotic neurons suggests that PV can persist in neurons of patients who have survived poliomyelitis.

Full Text

The Full Text of this article is available as a PDF (798.4 KB).

Selected References

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

  1. Agol V. I., Drozdov S. G., Ivannikova T. A., Kolesnikova M. S., Korolev M. B., Tolskaya E. A. Restricted growth of attenuated poliovirus strains in cultured cells of a human neuroblastoma. J Virol. 1989 Sep;63(9):4034–4038. doi: 10.1128/jvi.63.9.4034-4038.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Benton P. A., Murphy J. W., Lloyd R. E. K562 cell strains differ in their response to poliovirus infection. Virology. 1995 Oct 20;213(1):7–18. doi: 10.1006/viro.1995.1541. [DOI] [PubMed] [Google Scholar]
  3. Blondel B., Akacem O., Crainic R., Couillin P., Horodniceanu F. Detection by monoclonal antibodies of an antigenic determinant critical for poliovirus neutralization present on VP1 and on heat-inactivated virions. Virology. 1983 Apr 30;126(2):707–710. doi: 10.1016/s0042-6822(83)80027-0. [DOI] [PubMed] [Google Scholar]
  4. Blondel B., Crainic R., Fichot O., Dufraisse G., Candrea A., Diamond D., Girard M., Horaud F. Mutations conferring resistance to neutralization with monoclonal antibodies in type 1 poliovirus can be located outside or inside the antibody-binding site. J Virol. 1986 Jan;57(1):81–90. doi: 10.1128/jvi.57.1.81-90.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Borzakian S., Pelletier I., Calvez V., Colbere-Garapin F. Precise missense and silent point mutations are fixed in the genomes of poliovirus mutants from persistently infected cells. J Virol. 1993 May;67(5):2914–2917. doi: 10.1128/jvi.67.5.2914-2917.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bottenstein J. E., Sato G. H. Growth of a rat neuroblastoma cell line in serum-free supplemented medium. Proc Natl Acad Sci U S A. 1979 Jan;76(1):514–517. doi: 10.1073/pnas.76.1.514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Buc-Caron M. H. Neuroepithelial progenitor cells explanted from human fetal brain proliferate and differentiate in vitro. Neurobiol Dis. 1995 Feb;2(1):37–47. doi: 10.1006/nbdi.1995.0004. [DOI] [PubMed] [Google Scholar]
  8. Calvez V., Pelletier I., Borzakian S., Colbère-Garapin F. Identification of a region of the poliovirus genome involved in persistent infection of HEp-2 cells. J Virol. 1993 Jul;67(7):4432–4435. doi: 10.1128/jvi.67.7.4432-4435.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Calvez V., Pelletier I., Couderc T., Pavio-Guédo N., Blondel B., Colbère-Garapin F. Cell clones cured of persistent poliovirus infection display selective permissivity to the wild-type poliovirus strain Mahoney and partial resistance to the attenuated Sabin 1 strain and Mahoney mutants. Virology. 1995 Oct 1;212(2):309–322. doi: 10.1006/viro.1995.1488. [DOI] [PubMed] [Google Scholar]
  10. Calvez V., Pelletier I., Guedo N., Borzakian S., Couderc T., Blondel B., Colbere-Garapin F. Persistent poliovirus infection: development of new models with cell lines. Ann N Y Acad Sci. 1995 May 25;753:370–373. doi: 10.1111/j.1749-6632.1995.tb27564.x. [DOI] [PubMed] [Google Scholar]
  11. Carp R. I. Persistent infection of human lymphoid cells with poliovirus and development of temperature-sensitive mutants. Intervirology. 1981;15(1):49–56. doi: 10.1159/000149214. [DOI] [PubMed] [Google Scholar]
  12. Colbère-Garapin F., Christodoulou C., Crainic R., Pelletier I. Persistent poliovirus infection of human neuroblastoma cells. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7590–7594. doi: 10.1073/pnas.86.19.7590. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Colston E. M., Racaniello V. R. Poliovirus variants selected on mutant receptor-expressing cells identify capsid residues that expand receptor recognition. J Virol. 1995 Aug;69(8):4823–4829. doi: 10.1128/jvi.69.8.4823-4829.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Couderc T., Guédo N., Calvez V., Pelletier I., Hogle J., Colbère-Garapin F., Blondel B. Substitutions in the capsids of poliovirus mutants selected in human neuroblastoma cells confer on the Mahoney type 1 strain a phenotype neurovirulent in mice. J Virol. 1994 Dec;68(12):8386–8391. doi: 10.1128/jvi.68.12.8386-8391.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Dalakas M. C. New neuromuscular symptoms in patients with old poliomyelitis: a three-year follow-up study. Eur Neurol. 1986;25(5):381–387. doi: 10.1159/000116038. [DOI] [PubMed] [Google Scholar]
  16. Dalakas M. C. The post-polio syndrome as an evolved clinical entity. Definition and clinical description. Ann N Y Acad Sci. 1995 May 25;753:68–80. doi: 10.1111/j.1749-6632.1995.tb27532.x. [DOI] [PubMed] [Google Scholar]
  17. Eddé B., Jakob H., Darmon M. Two specific markers for neural differentiation of embryonal carcinoma cells. EMBO J. 1983;2(9):1473–1478. doi: 10.1002/j.1460-2075.1983.tb01610.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Fichot O., Girard M. An improved method for sequencing of RNA templates. Nucleic Acids Res. 1990 Oct 25;18(20):6162–6162. doi: 10.1093/nar/18.20.6162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. HOLLAND J. J. Receptor affinities as major determinants of enterovirus tissue tropisms in humans. Virology. 1961 Nov;15:312–326. doi: 10.1016/0042-6822(61)90363-4. [DOI] [PubMed] [Google Scholar]
  20. 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]
  21. Iizuka N., Kohara M., Hagino-Yamagishi K., Abe S., Komatsu T., Tago K., Arita M., Nomoto A. Construction of less neurovirulent polioviruses by introducing deletions into the 5' noncoding sequence of the genome. J Virol. 1989 Dec;63(12):5354–5363. doi: 10.1128/jvi.63.12.5354-5363.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. 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]
  24. Lendahl U., Zimmerman L. B., McKay R. D. CNS stem cells express a new class of intermediate filament protein. Cell. 1990 Feb 23;60(4):585–595. doi: 10.1016/0092-8674(90)90662-x. [DOI] [PubMed] [Google Scholar]
  25. Leon-Monzon M. E., Dalakas M. C. Detection of poliovirus antibodies and poliovirus genome in patients with the post-polio syndrome. Ann N Y Acad Sci. 1995 May 25;753:208–218. doi: 10.1111/j.1749-6632.1995.tb27547.x. [DOI] [PubMed] [Google Scholar]
  26. Leparc I., Kopecka H., Fuchs F., Janatova I., Aymard M., Julien J. Search for poliovirus in specimens from patients with the post-polio syndrome. Ann N Y Acad Sci. 1995 May 25;753:233–236. doi: 10.1111/j.1749-6632.1995.tb27549.x. [DOI] [PubMed] [Google Scholar]
  27. 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]
  28. McAllister A., Tangy F., Aubert C., Brahic M. Genetic mapping of the ability of Theiler's virus to persist and demyelinate. J Virol. 1990 Sep;64(9):4252–4257. doi: 10.1128/jvi.64.9.4252-4257.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Minor P. D., Pipkin P. A., Hockley D., Schild G. C., Almond J. W. Monoclonal antibodies which block cellular receptors of poliovirus. Virus Res. 1984;1(3):203–212. doi: 10.1016/0168-1702(84)90039-x. [DOI] [PubMed] [Google Scholar]
  30. Morrison M. E., He Y. J., Wien M. W., Hogle J. M., Racaniello V. R. Homolog-scanning mutagenesis reveals poliovirus receptor residues important for virus binding and replication. J Virol. 1994 Apr;68(4):2578–2588. doi: 10.1128/jvi.68.4.2578-2588.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Muir P., Nicholson F., Sharief M. K., Thompson E. J., Cairns N. J., Lantos P., Spencer G. T., Kaminski H. J., Banatvala J. E. Evidence for persistent enterovirus infection of the central nervous system in patients with previous paralytic poliomyelitis. Ann N Y Acad Sci. 1995 May 25;753:219–232. doi: 10.1111/j.1749-6632.1995.tb27548.x. [DOI] [PubMed] [Google Scholar]
  32. 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]
  33. Pelletier I., Couderc T., Borzakian S., Wyckoff E., Crainic R., Ehrenfeld E., Colbere-Garapin F. Characterization of persistent poliovirus mutants selected in human neuroblastoma cells. Virology. 1991 Feb;180(2):729–737. doi: 10.1016/0042-6822(91)90086-q. [DOI] [PubMed] [Google Scholar]
  34. Pilipenko E. V., Gmyl A. P., Maslova S. V., Svitkin Y. V., Sinyakov A. N., Agol V. I. Prokaryotic-like cis elements in the cap-independent internal initiation of translation on picornavirus RNA. Cell. 1992 Jan 10;68(1):119–131. doi: 10.1016/0092-8674(92)90211-t. [DOI] [PubMed] [Google Scholar]
  35. Raff M. C., Miller R. H., Noble M. A glial progenitor cell that develops in vitro into an astrocyte or an oligodendrocyte depending on culture medium. Nature. 1983 Jun 2;303(5916):390–396. doi: 10.1038/303390a0. [DOI] [PubMed] [Google Scholar]
  36. Sabaté O., Horellou P., Vigne E., Colin P., Perricaudet M., Buc-Caron M. H., Mallet J. Transplantation to the rat brain of human neural progenitors that were genetically modified using adenoviruses. Nat Genet. 1995 Mar;9(3):256–260. doi: 10.1038/ng0395-256. [DOI] [PubMed] [Google Scholar]
  37. Sharief M. K., Hentges R., Ciardi M. Intrathecal immune response in patients with the post-polio syndrome. N Engl J Med. 1991 Sep 12;325(11):749–755. doi: 10.1056/NEJM199109123251101. [DOI] [PubMed] [Google Scholar]
  38. Tucker R. P. The roles of microtubule-associated proteins in brain morphogenesis: a review. Brain Res Brain Res Rev. 1990 May-Aug;15(2):101–120. doi: 10.1016/0165-0173(90)90013-e. [DOI] [PubMed] [Google Scholar]
  39. de la Torre J. C., Dávila M., Sobrino F., Ortín J., Domingo E. Establishment of cell lines persistently infected with foot-and-mouth disease virus. Virology. 1985 Aug;145(1):24–35. doi: 10.1016/0042-6822(85)90198-9. [DOI] [PubMed] [Google Scholar]
  40. van der Werf S., Wychowski C., Bruneau P., Blondel B., Crainic R., Horodniceanu F., Girard M. Localization of a poliovirus type 1 neutralization epitope in viral capsid polypeptide VP1. Proc Natl Acad Sci U S A. 1983 Aug;80(16):5080–5084. doi: 10.1073/pnas.80.16.5080. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES