Skip to main content
NCBI home page
Wiley - PMC COVID-19 Collection logoLink to Wiley - PMC COVID-19 Collection
. 2005 Feb 4;32(3):215–229. doi: 10.1002/jemt.1070320305

Two models of multiple sclerosis: Experimental allergic encephalomyelitis (EAE) and theiler's murine encephalomyelitis virus (TMEV) infection. A pathological and immunological comparison

Mauro C Dal Canto 1,✉, Roger W Melvold 2, Byung S Kim 2, Stephen D Miller 2
PMCID: PMC7166956  PMID: 8527856

Abstract

Theiler's murine encephalomyelitis virus (TMEV) infection and experimental allergic encephalomyelitis (EAE) are considered among the best models of human multiple sclerosis (MS). In both models, clinical disease is characterized by paralysis, while pathological changes consist of inflammatory demyelination. In both models there is a genetic influence on susceptibility/resistance to the development of disease. This has been thoroughly studied in TMEV infection, and it has been found to depend on both major histocompatibility complex (MHC) and non‐MHC genes. At least four genes have been so far identified. Because of this genetic influence, some strains of mice are more susceptible to both clinical and pathological changes than others, and susceptibility appears to best correlate with the ability of a certain murine strain to develop a delayed‐type hypersensitivity (DTH) response to viral antigens. We have also observed that even among mice which are equally susceptible clinically, striking differences may be seen under pathological examination. These consist of different gradients of severity of inflammation, particularly in regards to the macrophage component. There is an inverse relationship between the number of macrophages, and their length of stay in the CNS, and the ability of mice to remyelinate their lesions. The most severe lesions are in SJL/J mice, and remyelination in this strain is extremely poor. The least severe lesions in terms of macrophage invasion are in strains such as NZW and RIIIS/J, and these are able to remyelinate lesions very successfully. Murine chronic relapsing EAE (CR‐EAE) shows pathological changes in many ways similar to those in TMEV‐infected SJL/J mice, although less severe in terms of degrees of macrophage infiltration and tissue destruction. Mice with CR‐EAE have a correspondingly limited ability to remyelinate their lesions. In both models the pathology appears to be mediated through a DTH response. However, while in EAE the DTH response is clearly against neuroantigens, the response in TMEV infection is against the virus itself. The end result in both models would be that of myelin destruction through a lymphotoxincytokine‐mediated mechanism. The importance of the DTH response in both models is well illustrated by the effects of tolerance induction in EAE and TMEV infection to neuroantigens and virus, respectively. These are important models of human MS, since the current hypothesis is that a viral infection early in life, on the appropriate genetic background, may trigger a secondary misdirected immune response which could be directed either against myelin antigens and/or possible persistent virus(es). © 1995 Wiley‐Liss, Inc.

Keywords: EAE, TMEV, Demyelination, Remyelination, Multiple sclerosis, Oligodendrocyte, Schwann cell

References

  1. Adams, R. D. (1959) A comparison of the morphology of the human demyelinative disease and experimental “allergic” encephalomyelitis In: “Allergic” Encephalomyelitys. Kies M. W. and Alvord E. C., eds. Charles C. Thomas, Springfield, IL, pp. 183–209. [Google Scholar]
  2. Barbano, R. L. , and Dal Canto, M. C. (1984) Serum and cells from Theiler's virus‐infected mice fail to injure myelinating cultures or to produce in vivo transfer of disease. The pathogenesis of Theiler's virus‐induced demyelination appears to differ from that of EAE. J. Neurol. Sci., 66: 283–293. [DOI] [PubMed] [Google Scholar]
  3. Blankenhorn, E. P. , and Stranford, S. A. (1992) Genetic factors in demyelinating diseases: Genes that control demyelination due to experimental allergic encephalomyelitis (EAE) and Theiler's murine encephalomyelitis virus. Reg. Immunol., 4: 331–343. [PubMed] [Google Scholar]
  4. Brown, A. M. , and McFarlin, D. E. (1981) Relapsing experimental allergic encephalomyelitis in SJL mouse. Lab. Invest., 45: 278–284. [PubMed] [Google Scholar]
  5. Brown, A. M. , McFarlin, D. E. , and Raine, C. S. (1982) Chronologic neuropathology of relapsing experimental allergic encephalomyelitis in the mouse. Lab. Invest., 46: 171–185. [PubMed] [Google Scholar]
  6. Bureau, J. F. , Montagutelli, X. , Lefebre, S. , Guenet, J.‐L. , Pla, M. , and Brahic, M. (1992) The interaction of two groups of murine genes determines the persistence of Theiler's virus in the central nervous system. J. Virol., 66: 4698–4704. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Chou, Y. K. , Bourdette, D. N. , Offner, H. , Whitham, R. , Wang, R.‐Y. , Hashim, G. A. , and Vandenbark, A. A. (1992) Frequency of T cells specific for myelin basic protein and myelin proteolipid protein in blood and cerebrospinal fluid in multiple sclerosis. J. Neuroimmunol., 38: 105–114. [DOI] [PubMed] [Google Scholar]
  8. Clatch, R. J. , Melvold, R. W. , Miller, S. D. , and Lipton, H. L. (1985) Theiler's murine encephalo myelitis virus (TMEV)–induced demyelinating disease in mice is influenced by the H‐2D region: Correlation with TMEV‐specific delayed‐type hypersensitivity. J. Immunol., 135: 1408–1414. [PubMed] [Google Scholar]
  9. Clatch, R. J. , Lipton, H. L. , and Miller, S. D. (1986) Characterization of Theiler's murine encephalomyelitis virus (TMEV)–specific delayedtype hypersensitivity responses in TMEV‐induced demyelinating disease: Correlation with clinical signs. J. Immunol., 136: 920–927. [PubMed] [Google Scholar]
  10. Clatch, R. J. , Melvold, R. W. , Dal Canto, M. C. , Miller, S. D. , and Lipton, H. L. (1987a) The Theiler's murine encephalomyelitis virus (TMEV) model for multiple sclerosis shows a strong influence of the murine equivalents of HLA‐A, B and C. J. Neuroimmunol., 15: 121–135. [DOI] [PubMed] [Google Scholar]
  11. Clatch, R. J. , Lipton, H. L. , and Miller, S. D. (1987b) Class II restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)–induced demyelinating disease. II. Survey of host immune responses and central nervous system titers in inbred mouse strains Microb. Pathog., 3: 327–337. [DOI] [PubMed] [Google Scholar]
  12. Clatch, R. J. , Miller, S. D. , Metzner, R. , Dal Canto, M. C. , and Lipton, H. L. (1990) Monocytes/macrophages isolated from the mouse CNS contain infectious Theiler's murine encephalomyelitis virus (TMEV). Virology, 176: 244–254. [DOI] [PubMed] [Google Scholar]
  13. Dal Canto, M. C. (1990) Experimental models of virus‐induced demyelination In: Handbook of Multiple Sclerosis. Cook S. M., ed. Marcel Dekker, Inc., New York and Basel, pp. 63–100. [Google Scholar]
  14. Dal Canto, M. C. , and Lipton, H. L. (1975) Primary demyelination in Theiler's virus infection. Lab. Invest., 33: 626–637. [PubMed] [Google Scholar]
  15. Dal Canto, M. C. , Wisniewski, H. , Johnson, A. B. , Brostoff, S. , and Raine, C. S. (1975) Vesicular disruption of myelin in autoimmune demyelination. J. Neurol. Sci., 24: 313–319. [DOI] [PubMed] [Google Scholar]
  16. Epstein, L. G. , Prineas, J. W. , and Raine, C. S. (1983) Attachment of myelin to coated pits on macrophages in experimental allergic encephalomyelitis. J. Neurol. Sci., 61: 341–348. [DOI] [PubMed] [Google Scholar]
  17. Fallis, R. J. , Raine, C. S. , and McFarlin, D. E. (1989) Chronic relapsing experimental allergic encephalomyelitis in SJL mice following the adoptive transfer of an epitope‐specific T cell line. J. Neuroimmunol., 22: 93–105. [DOI] [PubMed] [Google Scholar]
  18. Finkelman, F. D. , Holmes J., Katona, I. M. , Urban, J. F. Jr. , Beckmann, M. P. , Park, L. S. , Schooley, K. A. , Coffman, R. L. , Mosmann, T. R. , and Paul, W. E. (1990) Lymphokine control of in vivo immunoglobulin isotype selection. Annu. Rev. Immunol., 8: 303–333. [DOI] [PubMed] [Google Scholar]
  19. Friedmann, A. , Frankel, G. , Lorch, Y. , and Steinman L. (1987) Monoclonal anti‐I‐A antibody reverses chronic paralysis and demyelination in Theiler's virus–infected mice: Critical importance of timing of treatment. J. Virol., 61: 898–903. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Fritz, R. B. , and McFarlin, D. E. (1989) Encephalitogenic epitopes of myelin basic protein In: Chemical Immunology, Vol. 46 Sercarz E., ed. Karger, Basel, pp. 101–125. [PubMed] [Google Scholar]
  21. Gerety, S. J. , Rundell, M. K. , Dal Canto, M. C. , and Miller, S. D. (1994) Class II restricted T cell responses in Theiler's murine encephalomyelitis virus‐induced demyelinating disease. VI. Potentiation of demyelination with and characterization of an immunopathologic CD4+ T cell line specific for an immunodominant VP2 epitope. J. Immunol., 152: 919–929. [PubMed] [Google Scholar]
  22. Hofman, F. M. , Hinton, D. R. , Johnson, K. , and Merril J. E. (1989) Tumor necrosis factor identified in multiple sclerosis brain. J. Exp. Med., 170: 607–612. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Jenkins, M. K. , Pardoll, D. M. , Mizuguchi, J. , Quill, H. , and Schwartz, R. H. (1987) T cell unresponsiveness in vivo and in vitro: Fine specificity of induction and molecular characterization of the unresponsive state. Immunol. Rev., 95: 113–135. [DOI] [PubMed] [Google Scholar]
  24. Kappel, C. A. , Melvold, R. W. , and Kim, B. S. (1990) Influence of sex on susceptibility in the Theiler's murine encephalomyelitis virus model for multiple sclerosis. J. Neuroimmunol., 29: 15–19. [DOI] [PubMed] [Google Scholar]
  25. Kappel, C. A. , Dal Canto, M. C. , Melvold, R. W. , and Kim, B. S. (1991) Hierarchy of effects of the MHC and T cell receptor b‐chain genes in susceptibility to Theiler's murine encephalomyelitis virus–induced demyelinating disease. J. Immunol., 147: 4322–4326. [PubMed] [Google Scholar]
  26. Karpus, W. J. , Pope, J. G. , Peterson J. D., Dal Canto, M. C. , and Miller S. D. (in press) Inhibition of Theiler's virus‐mediated demyelination by peripheal immune tolerance induction. J. Immunol. [PubMed]
  27. Kennedy, M. K. , Dal Canto, M. C. , Trotter, J. L. , and Miller, S. D. (1988) Specific immune regulation of chronic relapsing experimental allergic encephalomyelitis in mice. J. Immunol., 141: 2986–2993. [PubMed] [Google Scholar]
  28. Kennedy, M. K. , Tan, L.‐J. , Dal Canto, M. C. , and Miller, S. D. (1990) Regulation of the effector stages of experimental autoimmune encephalomyelitis via neuroantigen‐specific tolerance induction. J. Immunol., 145: 117–126. [PubMed] [Google Scholar]
  29. Kurtzke, J. , and Hyllested, J. (1979) Multiple sclerosis in the Faroe Islands. I. Clinical and epidemiological features. Ann. Neurol., 5: 6–21. [DOI] [PubMed] [Google Scholar]
  30. Lipton, H. L. (1975) Theiler's virus infection in mice: An unusual biphasic disease process leading to demyelination. Infect. Immun. 11: 1147–1155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Lipton, H. L. (1980) Persistent Theiler's murine encephalomyelitis virus infection in mice depends on plaque size. J. Gen. Virol., 46: 169–177. [DOI] [PubMed] [Google Scholar]
  32. Lipton, H. L. , and Dal Canto, M. C. (1976) Theiler's virus–induced demyelination: Prevention by immunosuppression. Science, 192: 62–64. [DOI] [PubMed] [Google Scholar]
  33. Lipton, H. L. , and Dal Canto, M. C. (1979) Susceptibility of inbred miet to chronic central nervous system infection by Theiler's murine encephalomyelitis virus. Infect. Immun., 26: 369–374. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Lipton, H. L. , Kratochvil, J. , Sethi, P. , and Dal Canto, M. C. (1984) Theiler's virus antigen detected in mouse spinal cord 2 1/2 years after infection. Neurology, 34: 1117–1119. [DOI] [PubMed] [Google Scholar]
  35. Lublin, F. D. , Maurer, P. H. , Berry, R. G. , and Tippett, D. (1981) Delayed relapsing experimental allergic encephalomyelitis in mice. J. Immunol., 126: 819–822. [PubMed] [Google Scholar]
  36. Martin, R. , McFarland, H. F. , and McFarlin, D. E. (1992) Immunological aspects of demyelinating diseases. Annu. Rev. Immunol., 10: 153–187. [DOI] [PubMed] [Google Scholar]
  37. McRae, B. L. , Kennedy, M. K. , Tan, L.‐J. , Dal Canto, M. C. , and Miller, S. D. (1992) Induction of active and adoptive chronic relapsing experimental autoimmune encephalomyelitis (EAE) using an encephalitogenic epitope of proteolipid protein. J. Neuroimmunol., 38: 229–240. [DOI] [PubMed] [Google Scholar]
  38. Melvold, R. W. , Jokinen, D. M. , Knobler, R. and Lipton, H. L. (1987) Variations in genetic control of susceptibility to Theiler's murine encephalomyelitis virus (TMEV)–induced demyelinating disease. I. Differences between susceptible SJL/J and resistant BALB/c strain map near the T cell beta chain constant genes on chromosome 6. J. Immunol., 138: 1429–1433. [PubMed] [Google Scholar]
  39. Melvold, R. W. , Jokinen, D. M. , Miller, S. D. , Dal Canto, M. C. , and Lipton, H. L. (1990) Identification of a locus on mouse chromosome 3 involved in differential susceptibility to Theiler's murine encephalomyelitis virus (TMEV)–induced demyelinating disease. J. Virol., 64: 686–690. [DOI] [PMC free article] [PubMed] [Google Scholar]
  40. Miller, S. D. , Clatch, R. J. , Pevear, D. C. , Trotter, J. L. , and Lipton, H. L. (1987) Class II restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)–induced demyelinating disease. I Cross specificity among TMEV substrains and related picornaviruses, but not myelin proteins J. Immunol., 138: 3776–3784. [PubMed] [Google Scholar]
  41. Miller, S. D. , Gerety, S. J. , Kennedy, M. K. , Peterson, J. D. , Trotter, J. L. , Touhy, V. K. , Waltenbaugh, C. , Dal Canto, M. C. , and Lipton, H. L. (1990) Class II restricted T cell responses in Theiler's murine encephalomyelitis virus (TMEV)–induced demylinating disease. III. Failure of neuroantigen‐specific immune tolerance to affect the clinical course of demyelination J. Neuroimmunol., 26: 9–23. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Miller, S. D. , Tan, L.‐J. , Pope, L. , McRae, B. , and Karpus, W. J. (1992) Antigen‐specific tolerance as a therapy for experimental autoimmune encephalomyelitis. Int. Rev. Immunol., 9: 203–222. [DOI] [PubMed] [Google Scholar]
  43. Mokhtarian, F. , McFarlin, D. E. , and Raine, C. S. (1984) Adoptive transfer of myelin basic protein‐sensitized T cells produces chronic relapsing demyelinating disease in mice. Nature, 309: 356–358. [DOI] [PubMed] [Google Scholar]
  44. Moore, G. R. W. , and Raine, C. S. (1988) Immunogold localization and analysis of IgG in acute experimental allergic encephalomyelitis. Lab. Invest., 59: 641–648. [PubMed] [Google Scholar]
  45. Mosmann, T. R. , and Coffman, R. L. (1989) Th1 and Th2 cells: Different patterns of lymphokine secretion lead to different functional properties. Annu. Rev. immunol., 7: 145–174. [DOI] [PubMed] [Google Scholar]
  46. Nicholson, S. M. , Peterson, J. D. , Miller, S. D. , Wang, K. , Dal Canto, M. C. , and Melvold, R. W. (1994) BALB/c substain differences in susceptibility to Theiler's murine encephalomyelitis virus‐induced demyelinating disease. J. Neuroimmunol., 52: 19–24. [DOI] [PubMed] [Google Scholar]
  47. Patick, A. K. , Pease, L. R. , David, C. S. , and Rodriguez, M. (1990) Major histocompatibility complex‐conferred resistance to Theiler's virus‐induced demyelinating disease is inherited as a dominant trait in B10 congenic mice. J. Virol., 64: 5570–5576. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Peterson, J. D. , Waltenbaugh, C. , and Miller, S. D. (1992) IgG subclass responses to Theiler's murine encephalomyelitis virus infection and immunization suggest a dominant role for Th1 cells in susceptible mouse strains. Immunology, 75: 652–658. [PMC free article] [PubMed] [Google Scholar]
  49. Peterson, J. D. , Karpus, W. J. , Clatch, R. J. , and Miller, S. D. (1993) Split tolerance of Th1 and Th2 cells in tolerance to Theiler's murine encephalomyelitis virus. Eur. J. Immunol., 23: 46–55. [DOI] [PubMed] [Google Scholar]
  50. Pettinelli, C. B. , and McFarlin, D. E. (1981) Adoptive transfer of experimental allergic encephalomyelitis in SJL/J mice after in vitro activation of lymph node cells by myelin basic protein: Requirement for Lyt 1+ 2− T lymphocytes. J. Immunol., 127: 1420–1423. [PubMed] [Google Scholar]
  51. Pevear, D. C. , Calenoff, M. , Rozhon, E. , and Lipton, H. L. (1987) Analysis of the complete nucleotide sequence of the picornavirus Theiler's murine encephalomyelitis virus indicates that it is closely related to cardioviruses. J. Virol., 61: 1507–1516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Poser, C. M. (1993) The pathogenesis of multiple sclerosis. Additional considerations. J. Neurol. Sci., 115 (Suppl.): S3–15. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Prineas, J. W. (1985) The neuropathology of multiple sclerosis In: Handbook of Clinical Neurology, Vol. 3 Vinken P. J., Bruyn G. W., and Klawans H. L., eds. Elsevier Science Publishers, Amsterdam and New York, pp. 213–257. [Google Scholar]
  54. Prineas, J. W. , Barnard, R. O. , Revesz, T. , Kwon, E. E. , Sharer, L. , and Cho, E.‐S. (1993) Multiple sclerosis. Pathology of recurrent lesions. Brain, 116: 681–693. [DOI] [PubMed] [Google Scholar]
  55. Raine, C. S. (1991) Multiple sclerosis: A pivotal role for the T cell in lesion development. Neuropathol. Appl. Neurobiol., 17: 265–274. [DOI] [PubMed] [Google Scholar]
  56. Raine, C. S. , and Scheinberg, L. C. (1988) On the immunopathology of plaque development and repair in multiple sclerosis. J. Neuroimmunol., 120: 180–201. [DOI] [PubMed] [Google Scholar]
  57. Raine, C. S. , Snyder D. H., Valsamis, M. P. , and Stone, S. H. (1974) Chronic experimental allergic encephalomyelitis in inbred guinea pigs—an ultrastructural study. Lab. Invest., 31: 369–380. [PubMed] [Google Scholar]
  58. Raine, C. S. , Moktharian, F. , and McFarlin, D. E. (1984) Adoptively transferred chronic relapsing experimental autoimmune encephalomyelitis in the mouse. Neuropathological analysis. Lab. Invest., 51: 534–546. [PubMed] [Google Scholar]
  59. Rodriguez, M. , and David, C. S. (1985) Demyelination induced by Theiler's virus: Influence of the H‐2 complex. J. Immunol., 135: 2145–2148. [PubMed] [Google Scholar]
  60. Rodriguez, M. , Leibowitz, J. , and David, C. S. (1986a) Susceptibility to Theiler's virus–induced demyelination. Mapping of the gene within the H‐2D region. J. Exp. Med., 163: 620–631. [DOI] [PMC free article] [PubMed] [Google Scholar]
  61. Rodriguez, M. , Lafuse, W. P. , Leibowitz, J. , and David, C. S. (1986b) Partial suppression of Theiler's virus–induced demyelination in vivo by administration of monoclonal antibodies to immune‐response gene products (Ia antigens). Neurology, 36: 964–970. [DOI] [PubMed] [Google Scholar]
  62. Rodriguez, M. , Pease, L. R. , and David, C. S. (1986c) Immune‐mediated injury of virus‐infected oligodendrocytes. Immunol. Today, 7: 359–363. [DOI] [PubMed] [Google Scholar]
  63. Rodriguez, M. , Patick, A. K. , and Pease, L. R. (1990) Abrogation of resistance to Theiler's virus–induced demyelination in C57BL mice by total body irradiation. J. Neuroimmunol., 26: 189–199. [DOI] [PubMed] [Google Scholar]
  64. Rodriguez, M. , Dunkel, A. J. , Thiemann, R. L. , Leibowitz, J. , Zijlstra, M. , and Jaenisch, R. (1993) Abrogation of resistance to Theiler's virus–induced demyelination in H‐2b mice deficient in beta2‐microglobulin. J. Immunol., 151: 266–276. [PubMed] [Google Scholar]
  65. Roos, R. P. , Firestone, S. , Wollmann, R. , Variakojis, D. , and Arnason, B. G. (1982) The effect of short‐term and chronic immunosuppression on Theiler's virus demyelination. J. Neuroimmunol., 2: 223–234. [DOI] [PubMed] [Google Scholar]
  66. Selmaj, K. , and Raine, C. S. (1988) Tumor necrosis factor mediates myelin and oligodendrocyte damage in vitro. Ann. Neurol., 23: 339–346. [DOI] [PubMed] [Google Scholar]
  67. Snapper, C. M. , and Paul, W. E. (1987) Interferon‐gamma and B cell stimulatory factor‐1 reciprocally regulate Ig isotype production. Science, 236: 944–947. [DOI] [PubMed] [Google Scholar]
  68. Tan, L.‐J. , Kennedy, M. K. , Dal Canto, M. C. , and Miller, S. D. (1991) Successful treatment of paralytic relapses in adoptive experimental autoimmune encephalomyelitis via neuroantigen‐specific tolerance. J. Immunol., 147: 1797–1802. [PubMed] [Google Scholar]
  69. Tan, L.‐J. , Kennedy, M. K. , and Miller, S. D. (1992) Regulation of the effector stages of experimental autoimmune encephalomyelitis via neuroantigen‐specific tolerance induction: II. Fine specificity of effector T cell inhibition J. Immunol., 148: 2748–2755. [PubMed] [Google Scholar]
  70. Theiler, M. (1937) Spontaneous encephalomyelitis of mice, a new virus disease. J. Exp. Med., 65: 705–719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Trotter, J. L. , Clark, H. B. , Collins, K. G. , Wegeschiede, C. L. , and Scarpellini, J. D. (1987) Myelin proteolipid protein induces demyelinating disease in mice. J. Neurol. Sci., 79: 173–188. [DOI] [PubMed] [Google Scholar]
  72. Tuohy, V. K. , Lu, Z. , Sobel, R. A. , Laursen R. A., and Lees, M. B. (1989) Identification of an encephalitogenic determinant of myelin proteolipid protein for SJL mice. J. Immunol., 142: 1523–1527. [PubMed] [Google Scholar]
  73. van der Veen, R. C. , Trotter, J. L. , Clark, H. B. , and Kapp J. A. (1989) The adoptive transfer of chronic relapsing experimental allergic encephalomyelitis with lymph node cells sensitized to myelin proteolipid protein. J. Neuroimmunol., 21: 183–191. [DOI] [PubMed] [Google Scholar]
  74. Welsh, C. J. , Tonks, P. , Nash, A. A. , and Blakemore, W F. (1987) The effect of L3T4 T cell depletion on the pathogenesis of Theiler's murine encephalomyelitis virus infection in CBA mice. J. Gen. Virol., 68: 1659–1667. [DOI] [PubMed] [Google Scholar]

Articles from Microscopy Research and Technique are provided here courtesy of Wiley

RESOURCES