Abstract
Poliovirus (PV) is the causal agent of paralytic poliomyelitis. Many survivors of the acute disease, after decades of clinical stability, develop new muscular symptoms called postpolio syndrome. It has been hypothesized that the persistence of PV in the spinal cord is involved in the etiology of this syndrome. To investigate the ability of PV to persist in the spinal cord after the onset of paralysis, we exploited a mouse model in which most animals inoculated with a mouse-adapted mutant survived after the onset of paralysis. Light microscopy and ultrastructural immunohistochemical studies and reverse transcription followed by nested PCR performed on spinal cord from paralyzed mice demonstrated that PV persisted in the mouse spinal cord for at least 12 months after the onset of paralysis. This mouse model provides a new tool for studying poliomyelitis evolution after the onset of paralysis.
Full Text
The Full Text of this article is available as a PDF (978.6 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adami C., Pooley J., Glomb J., Stecker E., Fazal F., Fleming J. O., Baker S. C. Evolution of mouse hepatitis virus (MHV) during chronic infection: quasispecies nature of the persisting MHV RNA. Virology. 1995 Jun 1;209(2):337–346. doi: 10.1006/viro.1995.1265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- BODIAN D. Emerging concept of poliomyelitis infection. Science. 1955 Jul 15;122(3159):105–108. doi: 10.1126/science.122.3159.105. [DOI] [PubMed] [Google Scholar]
- 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]
- 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]
- Campbell A. M., Williams E. R., Pearce J. Late motor neuron degeneration following poliomyelitis. Neurology. 1969 Nov;19(11):1101–1106. doi: 10.1212/wnl.19.11.1101. [DOI] [PubMed] [Google Scholar]
- Cash E., Chamorro M., Brahic M. Minus-strand RNA synthesis in the spinal cords of mice persistently infected with Theiler's virus. J Virol. 1988 May;62(5):1824–1826. doi: 10.1128/jvi.62.5.1824-1826.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cattaneo R., Schmid A., Eschle D., Baczko K., ter Meulen V., Billeter M. A. Biased hypermutation and other genetic changes in defective measles viruses in human brain infections. Cell. 1988 Oct 21;55(2):255–265. doi: 10.1016/0092-8674(88)90048-7. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Couderc T., Christodoulou C., Kopecka H., Marsden S., Taffs L. F., Crainic R., Horaud F. Molecular pathogenesis of neural lesions induced by poliovirus type 1. J Gen Virol. 1989 Nov;70(Pt 11):2907–2918. doi: 10.1099/0022-1317-70-11-2907. [DOI] [PubMed] [Google Scholar]
- Couderc T., Hogle J., Le Blay H., Horaud F., Blondel B. Molecular characterization of mouse-virulent poliovirus type 1 Mahoney mutants: involvement of residues of polypeptides VP1 and VP2 located on the inner surface of the capsid protein shell. J Virol. 1993 Jul;67(7):3808–3817. doi: 10.1128/jvi.67.7.3808-3817.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cunningham L., Bowles N. E., Lane R. J., Dubowitz V., Archard L. C. Persistence of enteroviral RNA in chronic fatigue syndrome is associated with the abnormal production of equal amounts of positive and negative strands of enteroviral RNA. J Gen Virol. 1990 Jun;71(Pt 6):1399–1402. doi: 10.1099/0022-1317-71-6-1399. [DOI] [PubMed] [Google Scholar]
- Dalakas M. C., Sever J. L., Madden D. L., Papadopoulos N. M., Shekarchi I. C., Albrecht P., Krezlewicz A. Late postpoliomyelitis muscular atrophy: clinical, virologic, and immunologic studies. Rev Infect Dis. 1984 May-Jun;6 (Suppl 2):S562–S567. doi: 10.1093/clinids/6.supplement_2.s562. [DOI] [PubMed] [Google Scholar]
- Jubelt B., Meagher J. B. Poliovirus infection of cyclophosphamide-treated mice results in persistence and late paralysis: I. Clinical, pathologic, and immunologic studies. Neurology. 1984 Apr;34(4):486–493. doi: 10.1212/wnl.34.4.486. [DOI] [PubMed] [Google Scholar]
- Jubelt B., Meagher J. B. Poliovirus infection of cyclophosphamide-treated mice results in persistence and late paralysis: II. Virologic studies. Neurology. 1984 Apr;34(4):494–499. doi: 10.1212/wnl.34.4.494. [DOI] [PubMed] [Google Scholar]
- Klingel K., Hohenadl C., Canu A., Albrecht M., Seemann M., Mall G., Kandolf R. Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):314–318. doi: 10.1073/pnas.89.1.314. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- 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]
- 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]
- 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]
- 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]
- Miller J. R. Prolonged intracerebral infection with poliovirus in asymptomatic mice. Ann Neurol. 1981 Jun;9(6):590–596. doi: 10.1002/ana.410090613. [DOI] [PubMed] [Google Scholar]
- 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]
- Oldstone M. B. Viral persistence. Cell. 1989 Feb 24;56(4):517–520. doi: 10.1016/0092-8674(89)90573-4. [DOI] [PubMed] [Google Scholar]
- Pavio N., Buc-Caron M. H., Colbère-Garapin F. Persistent poliovirus infection of human fetal brain cells. J Virol. 1996 Sep;70(9):6395–6401. doi: 10.1128/jvi.70.9.6395-6401.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
- Pezeshkpour G. H., Dalakas M. C. Long-term changes in the spinal cords of patients with old poliomyelitis. Signs of continuous disease activity. Arch Neurol. 1988 May;45(5):505–508. doi: 10.1001/archneur.1988.00520290033010. [DOI] [PubMed] [Google Scholar]
- 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]
- Sidhu M. S., Crowley J., Lowenthal A., Karcher D., Menonna J., Cook S., Udem S., Dowling P. Defective measles virus in human subacute sclerosing panencephalitis brain. Virology. 1994 Aug 1;202(2):631–641. doi: 10.1006/viro.1994.1384. [DOI] [PubMed] [Google Scholar]
- Wong T. C., Ayata M., Ueda S., Hirano A. Role of biased hypermutation in evolution of subacute sclerosing panencephalitis virus from progenitor acute measles virus. J Virol. 1991 May;65(5):2191–2199. doi: 10.1128/jvi.65.5.2191-2199.1991. [DOI] [PMC free article] [PubMed] [Google Scholar]