Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1982 Jan;106(1):20–29.

Ultrastructural immunohistochemical localization of virus in acute and chronic demyelinating Theiler's virus infection.

M C Dal Canto, H L Lipton
PMCID: PMC1915969  PMID: 6275708

Abstract

Mice experimentally infected with Theiler's murine encephalomyelitis virus (TMEV) develop a persistent infection of the central nervous system (CNS). The most striking feature of this infection is the occurrence of inflammatory primary demyelination in the spinal cord white matter. The pathogenesis of myelin degeneration in this model has not been clarified, but morphologic and immunologic data suggest that the host immune response plays a major role in the production of myelin injury. Because of low virus titers in infected adult mice and of the small size of TMEV, virus particles have never been observed in this demyelinating model. Yet elucidation of the types of cells in the CNS supporting virus replication would be important for a better understanding of both virus persistence and virus-induced demyelinating pathology. The present paper is a sequential study of the localization of TMEV in the spinal cord in infected mice by ultrastructural immunohistochemical techniques. Results indicate that virus replication is mainly in neurons during the acute phase of the disease, while in the chronic phase viral inclusions are mainly found in macrophages in and around demyelinating lesions. Other cells are also infected, but to a lesser degree. In the neuronal system both axoplasmic and dendritic flow appear to facilitate the spread of virus in the CNS. In macrophages, the presence of virus particles and the association of virus with altered components of the cytoskeleton support active virus production rather than simple internalization. The macrophage appears to play an important role in both the establishment of virus persistence and in the process of demyelination in this animal model.

Full text

PDF
20

Images in this article

22Figure 1 and 2
on p.22
23Figure 3 and 4
on p.23
23Figure 5
on p.23
24Figure 6
on p.24
24Figure 7
on p.24
25Figure 8
on p.25
25Figure 9
on p.25
27Figure 10-12
on p.27
27Figure 13
on p.27
28Figure 14
on p.28
28Figure 15 and 16
on p.28

Selected References

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

  1. Bell T. M., Field E. J., Narang H. K. Zika virus infection of the central nervous system of mice. Arch Gesamte Virusforsch. 1971;35(2):183–193. doi: 10.1007/BF01249709. [DOI] [PubMed] [Google Scholar]
  2. Brautigam A. R., Dutko F. J., Olding L. B., Oldstone M. B. Pathogenesis of murine cytomegalovirus infection: the macrophage as a permissive cell for cytomegalovirus infection, replication and latency. J Gen Virol. 1979 Aug;44(2):349–359. doi: 10.1099/0022-1317-44-2-349. [DOI] [PubMed] [Google Scholar]
  3. Cammer W., Bloom B. R., Norton W. T., Gordon S. Degradation of basic protein in myelin by neutral proteases secreted by stimulated macrophages: a possible mechanism of inflammatory demyelination. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1554–1558. doi: 10.1073/pnas.75.3.1554. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Dal Canto M. C., Lipton H. L. Multiple sclerosis. Animal model:Theiler's virus infection in mice. Am J Pathol. 1977 Aug;88(2):497–500. [PMC free article] [PubMed] [Google Scholar]
  5. Dal Canto M. C., Lipton H. L. Primary demyelination in Theiler's virus infection. An ultrastructural study. Lab Invest. 1975 Dec;33(6):626–637. [PubMed] [Google Scholar]
  6. Dal Canto M. C., Lipton H. L. Recurrent demyelination in chronic central nervous system infection produced by Theiler's murine encephalomyelitis virus. J Neurol Sci. 1979 Aug;42(3):391–405. doi: 10.1016/0022-510x(79)90172-2. [DOI] [PubMed] [Google Scholar]
  7. Dal Canto M. C., Lipton H. L. Schwann cell remyelination and recurrent demyelination in the central nervous system of mice infected with attenuated Theiler's virus. Am J Pathol. 1980 Jan;98(1):101–122. [PMC free article] [PubMed] [Google Scholar]
  8. Dal Canto M. C., Rabinowitz S. G., Johnson T. C., Hughes J. V. Ultrastructural-immunohistochemical evidence for a maturation defect of temperature-sensitive G31 vesicular stomatitis virus in murine spinal cord neurons. Infect Immun. 1979 Apr;24(1):276–281. doi: 10.1128/iai.24.1.276-281.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dubois-Dalcq M., McFarland H., McFarlin D. Protein A-peroxidase: a valluable tool for the localization of antigens. J Histochem Cytochem. 1977 Nov;25(11):1201–1206. doi: 10.1177/25.11.199666. [DOI] [PubMed] [Google Scholar]
  10. Kreutzberg G. W., Schubert P., Tóth L., Rieske E. Intradendritic transport to postsynaptic sites. Brain Res. 1973 Nov 23;62(2):399–404. doi: 10.1016/0006-8993(73)90702-6. [DOI] [PubMed] [Google Scholar]
  11. Kristensson K., Ghetti B., Wiśniewski H. M. Study on the propagation of Herpes simplex virus (type 2) into the brain after intraocular injection. Brain Res. 1974 Apr 5;69(2):189–201. doi: 10.1016/0006-8993(74)90001-8. [DOI] [PubMed] [Google Scholar]
  12. Lampert P. W. Autoimmune and virus-induced demyelinating diseases. A review. Am J Pathol. 1978 Apr;91(1):176–208. [PMC free article] [PubMed] [Google Scholar]
  13. Lenk R., Penman S. The cytoskeletal framework and poliovirus metabolism. Cell. 1979 Feb;16(2):289–301. doi: 10.1016/0092-8674(79)90006-0. [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. 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]
  16. Penney J. B., Jr, Wolinsky J. S. Neuronal and oligodendroglial infection by the WW strain of Theiler's virus. Lab Invest. 1979 Mar;40(3):324–330. [PubMed] [Google Scholar]
  17. Sternberger L. A., Hardy P. H., Jr, Cuculis J. J., Meyer H. G. The unlabeled antibody enzyme method of immunohistochemistry: preparation and properties of soluble antigen-antibody complex (horseradish peroxidase-antihorseradish peroxidase) and its use in identification of spirochetes. J Histochem Cytochem. 1970 May;18(5):315–333. doi: 10.1177/18.5.315. [DOI] [PubMed] [Google Scholar]
  18. Wardley R. C., Wilkinson P. J. The growth of virulent African swine fever virus in pig monocytes and macrophages. J Gen Virol. 1978 Jan;38(1):183–186. doi: 10.1099/0022-1317-38-1-183. [DOI] [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES