Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1985 Dec;56(3):887–895. doi: 10.1128/jvi.56.3.887-895.1985

Localization of a neutralization site of Theiler's murine encephalomyelitis viruses.

S Nitayaphan, M M Toth, R P Roos
PMCID: PMC252661  PMID: 2415718

Abstract

Theiler's murine encephalomyelitis viruses (TMEV) are picornaviruses that produce enteric and neurological diseases in mice. Subgroup TO strains of TMEV cause persistent infections with demyelination, while subgroup GDVII strains neither persist nor demyelinate. We produced neutralizing monoclonal antibodies (mAbs) to clarify the mechanisms of persistence and demyelination. Some of the neutralizing mAbs reacted with isolated VP1 on Western blots, while others were conformation specific. The neutralization site for the former TMEV mAbs was on the VP1 trypsin cleavage site of the intact virion. The neutralization site for the conformation-specific mAbs was distinct and was not affected by trypsin. Trypsin treatment of subgroup TO strains increased their infectivity for L cells, whereas the infectivity of subgroup GDVII strains was decreased by trypsin treatment. Subpopulations of virus in subgroup TO-infected tissue culture cells and in infected mouse brain homogenates contained VP1-cleaved virus; this VP1-cleaved virus gave rise to a large persistent fraction in neutralization tests when it was reacted with VP1-specific mAbs. These findings have implications regarding the pathogenesis of subgroup TO demyelinating disease. TMEV VP1 cleavage may be important for virus persistence because of disruption of a major neutralization epitope. The change in virus surface structure caused by VP1 cleavage may affect cell binding and lead to altered cytotropism. Immunocytes, which have been implicated in subgroup TO demyelination, may provide a source for proteases for VP1 cleavage.

Full text

PDF
887

Images in this article

888Image
on p.888
890Image
on p.890
890Image
on p.890
892Image
on p.892

Selected References

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

  1. Baxt B., Bachrach H. L. The adsorption and degradation of foot-and-mouth disease virus by isolated BHK-21 cell plasma membranes. Virology. 1982 Jan 30;116(2):391–405. doi: 10.1016/0042-6822(82)90134-9. [DOI] [PubMed] [Google Scholar]
  2. Baxt B., Morgan D. O., Robertson B. H., Timpone C. A. Epitopes on foot-and-mouth disease virus outer capsid protein VP1 involved in neutralization and cell attachment. J Virol. 1984 Aug;51(2):298–305. doi: 10.1128/jvi.51.2.298-305.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Buchmeier M. J., Lewicki H. A., Talbot P. J., Knobler R. L. Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology. 1984 Jan 30;132(2):261–270. doi: 10.1016/0042-6822(84)90033-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cash E., Chamorro M., Brahic M. Theiler's virus RNA and protein synthesis in the central nervous system of demyelinating mice. Virology. 1985 Jul 15;144(1):290–294. doi: 10.1016/0042-6822(85)90327-7. [DOI] [PubMed] [Google Scholar]
  5. Dal Canto M. C., Lipton H. L. Ultrastructural immunohistochemical localization of virus in acute and chronic demyelinating Theiler's virus infection. Am J Pathol. 1982 Jan;106(1):20–29. [PMC free article] [PubMed] [Google Scholar]
  6. Dal Canto M. C. Uncoupled relationship between demyelination and primary infection of myelinating cells in Theiler's virus encephalomyelitis. Infect Immun. 1982 Mar;35(3):1133–1138. doi: 10.1128/iai.35.3.1133-1138.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Docherty K., Steiner D. F. Post-translational proteolysis in polypeptide hormone biosynthesis. Annu Rev Physiol. 1982;44:625–638. doi: 10.1146/annurev.ph.44.030182.003205. [DOI] [PubMed] [Google Scholar]
  8. Duchesne M., Cartwright T., Crespo A., Boucher F., Fallourd A. Localization of a neutralization epitope of foot-and-mouth disease virus using neutralizing monoclonal antibodies. J Gen Virol. 1984 Sep;65(Pt 9):1559–1566. doi: 10.1099/0022-1317-65-9-1559. [DOI] [PubMed] [Google Scholar]
  9. Fricks C. E., Icenogle J. P., Hogle J. M. Trypsin sensitivity of the Sabin strain of type 1 poliovirus: cleavage sites in virions and related particles. J Virol. 1985 Jun;54(3):856–859. doi: 10.1128/jvi.54.3.856-859.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Iorio R. M., Bratt M. A. Neutralization of Newcastle disease virus by monoclonal antibodies to the hemagglutinin-neuraminidase glycoprotein: requirement for antibodies to four sites for complete neutralization. J Virol. 1984 Aug;51(2):445–451. doi: 10.1128/jvi.51.2.445-451.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Knudsen R. C., Groocock C. M., Andersen A. A. Protective role of foot-and-mouth disease virus antibody in vitro and in vivo in guinea-pigs. J Gen Virol. 1983 Feb;64(Pt 2):341–348. doi: 10.1099/0022-1317-64-2-341. [DOI] [PubMed] [Google Scholar]
  12. Lazarowitz S. G., Compans R. W., Choppin P. W. Proteolytic cleavage of the hemagglutinin polypeptide of influenza virus. Function of the uncleaved polypeptide HA. Virology. 1973 Mar;52(1):199–212. doi: 10.1016/0042-6822(73)90409-1. [DOI] [PubMed] [Google Scholar]
  13. Lehrich J. R., Arnason B. G., Hochberg F. H. Demyelinative myelopathy in mice induced by the DA virus. J Neurol Sci. 1976 Oct;29(2-4):149–160. doi: 10.1016/0022-510x(76)90167-2. [DOI] [PubMed] [Google Scholar]
  14. Lipton H. L., Dal Canto M. C. Theiler's virus-induced demyelination: prevention by immunosuppression. Science. 1976 Apr 2;192(4234):62–64. doi: 10.1126/science.176726. [DOI] [PubMed] [Google Scholar]
  15. Lipton H. L., Friedmann A. Purification of Theiler's murine encephalomyelitis virus and analysis of the structural virion polypeptides: correlation of the polypeptide profile with virulence. J Virol. 1980 Mar;33(3):1165–1172. doi: 10.1128/jvi.33.3.1165-1172.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lipton H. L., Gonzalez-Scarano F. Central nervous system immunity in mice infected with theiler's virus. I. Local neutralizing antibody response. J Infect Dis. 1978 Feb;137(2):145–151. doi: 10.1093/infdis/137.2.145. [DOI] [PubMed] [Google Scholar]
  17. Lipton H. L. Persistent Theiler's murine encephalomyelitis virus infection in mice depends on plaque size. J Gen Virol. 1980 Jan;46(1):169–177. doi: 10.1099/0022-1317-46-1-169. [DOI] [PubMed] [Google Scholar]
  18. Lipton H. L. Theiler's virus infection in mice: an unusual biphasic disease process leading to demyelination. Infect Immun. 1975 May;11(5):1147–1155. doi: 10.1128/iai.11.5.1147-1155.1975. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lorch Y., Friedmann A., Lipton H. L., Kotler M. Theiler's murine encephalomyelitis virus group includes two distinct genetic subgroups that differ pathologically and biologically. J Virol. 1981 Nov;40(2):560–567. doi: 10.1128/jvi.40.2.560-567.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Lorch Y., Friedmann A. Proteins induced in tissue culture by four isolates of Theiler's murine encephalomyelitis virus. J Virol. 1983 Feb;45(2):496–504. doi: 10.1128/jvi.45.2.496-504.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Lorch Y., Kotler M., Friedmann A. Persistent and acute central nervous system infections are caused by Theiler's murine encephalomyelitis viruses which differ in RNA composition but code for only slightly different proteins. J Virol. 1984 Dec;52(3):960–965. doi: 10.1128/jvi.52.3.960-965.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. MORRIS M. C. The effect of trypsin on hemagglutination by murine encephalomyelitis virus (GDVII). J Immunol. 1952 Jan;68(1):97–108. [PubMed] [Google Scholar]
  23. Narayan O., Wolinsky J. S., Clements J. E., Strandberg J. D., Griffin D. E., Cork L. C. Slow virus replication: the role of macrophages in the persistence and expression of visna viruses of sheep and goats. J Gen Virol. 1982 Apr;59(Pt 2):345–356. doi: 10.1099/0022-1317-59-2-345. [DOI] [PubMed] [Google Scholar]
  24. Nitayaphan S., Toth M. M., Roos R. P. Neutralizing monoclonal antibodies to Theiler's murine encephalomyelitis viruses. J Virol. 1985 Feb;53(2):651–657. doi: 10.1128/jvi.53.2.651-657.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Offit P. A., Clark H. F. Protection against rotavirus-induced gastroenteritis in a murine model by passively acquired gastrointestinal but not circulating antibodies. J Virol. 1985 Apr;54(1):58–64. doi: 10.1128/jvi.54.1.58-64.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Ouldridge E. J., Barnett P. V., Parry N. R., Syred A., Head M., Rweyemamu M. M. Demonstration of neutralizing and non-neutralizing epitopes on the trypsin-sensitive site of foot-and-mouth disease virus. J Gen Virol. 1984 Jan;65(Pt 1):203–207. doi: 10.1099/0022-1317-65-1-203. [DOI] [PubMed] [Google Scholar]
  27. Reagan K. J., Goldberg B., Crowell R. L. Altered receptor specificity of coxsackievirus B3 after growth in rhabdomyosarcoma cells. J Virol. 1984 Mar;49(3):635–640. doi: 10.1128/jvi.49.3.635-640.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Rodriguez M., Leibowitz J. L., Lampert P. W. Persistent infection of oligodendrocytes in Theiler's virus-induced encephalomyelitis. Ann Neurol. 1983 Apr;13(4):426–433. doi: 10.1002/ana.410130409. [DOI] [PubMed] [Google Scholar]
  29. Roos R. P., Firestone S., Wollmann R., Variakojis D., Arnason B. G. The effect of short-term and chronic immunosuppression on Theiler's virus demyelination. J Neuroimmunol. 1982 Jun;2(3-4):223–234. doi: 10.1016/0165-5728(82)90057-1. [DOI] [PubMed] [Google Scholar]
  30. Roos R. P., Richards O. C., Green J., Ehrenfeld E. Characterization of a cell culture persistently infected with the DA strain of Theiler's murine encephalomyelitis virus. J Virol. 1982 Sep;43(3):1118–1122. doi: 10.1128/jvi.43.3.1118-1122.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Roos R. P., Whitelaw P. J. Biochemical analysis of DA strain of Theiler's murine encephalomyelitis virus obtained directly from acutely infected mouse brain. Infect Immun. 1984 Jun;44(3):642–649. doi: 10.1128/iai.44.3.642-649.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Roos R. P., Wollmann R. DA strain of Theiler's murine encephalomyelitis virus induces demyelination in nude mice. Ann Neurol. 1984 May;15(5):494–499. doi: 10.1002/ana.410150516. [DOI] [PubMed] [Google Scholar]
  33. Ryder S. W., Straus E., Yalow R. S. Further characterization of brain cholecystokinin-converting enzymes. Proc Natl Acad Sci U S A. 1980 Jun;77(6):3669–3671. doi: 10.1073/pnas.77.6.3669. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. SHAW M. Serologic studies of Theiler's mouse encephalomyelitis virus. Proc Soc Exp Biol Med. 1956 Jun;92(2):390–390. doi: 10.3181/00379727-92-22487. [DOI] [PubMed] [Google Scholar]

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

RESOURCES