Skip to main content
PMC home page
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2002 May 1;8(3):257–264. doi: 10.1080/13550280290049697

Neither B cells nor T cells are required for CNS demyelination in mice persistently infected with MHV-A59

A E Matthews 1, E Lavi 2, S R Weiss 1, Y Paterson 1,✉
PMCID: PMC7095043  PMID: 12053280

Abstract

Murine hepatitis virus A59 infection of the central nervous system (CNS) results in CNS demyelination in susceptible strains of mice. In infected B-cell-deficient mice, demyelination not only occurred but was also more severe than in parental C57BL/6 animals. This increase may be due to the persistence of virus in the CNS in the absence of B cells. In mice lacking antibody receptors or complement pathway activity, virus did not persist yet demyelination was similar to parental mice. In infected RAG1−/− mice, moderately sized, typical demyelinating lesions were identified. Therefore, demyelination can occur in the absence of B and T cells.

Keywords: MHV-A59, demyelination, B cells, Fc receptor KO, complement KO

Footnotes

This work was supported by NIH grant AI-36657 (YP) and National Multiple Sclerosis Society grants RG2585 (SRW) and RG2615 (EL). AM was partially supported by T32-CA-EY-07131 and T32-GM-07170 (NIH Veterinary Medical Scientist Training Program).

References

  1. Barac-Latas V, Suchanek G, Breitschopf H, Stuehler A, Wege H, Lassmann H. Patterns of oligodendrocyte pathology in coronavirus-induced subacute demyelinating encephalomyelitis in the Lewis rat. Glia. 1997;19:1–12. doi: 10.1002/(SICI)1098-1136(199701)19:1<1::AID-GLIA1>3.0.CO;2-5. [DOI] [PubMed] [Google Scholar]
  2. Buchmeier MJ, Lewicki HA, Talbot PJ, Knobler RL. Murine hepatitis virus-4 (strain JHM)-induced neurologic disease is modulated in vivo by monoclonal antibody. Virology. 1984;132:261–270. doi: 10.1016/0042-6822(84)90033-3. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Circolo A, Garnier G, Fukuda W, Wang X, Hidvegi T, Szalai AJ, Briles DE, Volanakis JE, Wetsel RA, Colten HR. Genetic disruption of the murine complement C3 promoter region generates deficient mice with extrahepatic expression of C3 mRNA. Immunopharmacology. 1999;42:135–149. doi: 10.1016/S0162-3109(99)00021-1. [DOI] [PubMed] [Google Scholar]
  4. Das Sarma J, Fu L, Tsai JC, Weiss SR, Lavi E. Demyelination determinants map to the spike glycoprotein gene of coronavirus mouse hepatitis virus. J Virol. 2000;74:9206–9213. doi: 10.1128/JVI.74.19.9206-9213.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Fleming JO, Wang FI, Trousdale MD, Hinton DR, Stohlman SA. Interaction of immune and central nervous systems: contribution of anti-viral Thy-1+ cells to demyelination induced by coronavirus JHM. Reg Immunol. 1993;5:37–43. [PubMed] [Google Scholar]
  6. Gombold JL, Sutherland RM, Lavi E, Paterson Y, Weiss SR. Mouse hepatitis virus A59-induced demyelination in mice can occur in the absence of CD8+ T cells. Microb Pathogen. 1995;18:211–221. doi: 10.1016/S0882-4010(95)90058-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Herndon RM, Price DL, Weiner LP. Regeneration of oligodendroglia during recovery from demyelinating disease. Science. 1977;195:693–694. doi: 10.1126/science.190678. [DOI] [PubMed] [Google Scholar]
  8. Houtman JJ, Fleming JO. Dissociation of demyelination and viral clearance in congenitally immunodeficient mice infected with murine coronavirus JHM. J Neuro Virol. 1996;2:101–110. doi: 10.3109/13550289609146543. [DOI] [PubMed] [Google Scholar]
  9. Jordan CA, Friedrich VL, Godfraind C, Cardellechio CB, Holmes KV, Dubois-Dalcq M. Expression of viral and myelin gene transcripts in a murine CNS demyelinating disease caused by a coronavirus. Glia. 1989;2:318–329. doi: 10.1002/glia.440020505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Lampert PW, Sims JK, Kniazeff AJ. Mechanism of demyelination in JHM virus encephalomyelitis. Electron microscopic studies. Acta Neuropathol (Berl) 1973;24:76–85. doi: 10.1007/BF00691421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lavi E, Gilden DH, Wroblewska Z, Rorke LB, Weiss SR. Experimental demyelination produced by the A59 strain of mouse hepatitis virus. Neurology. 1984;34:597–603. doi: 10.1212/WNL.34.5.597. [DOI] [PubMed] [Google Scholar]
  12. Lavi E, Gilden DH, Highkin MK, Weiss SR. Persistence of mouse hepatitis virus A59 RNA in a slow virus demyelinating infection in mice as detected by in situ hybridization. J Virol. 1984;51:563–566. doi: 10.1128/jvi.51.2.563-566.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Linington C, Lassmann H. Antibody responses in chronic relapsing experimental allergic encephalomyelitis: correlation of serum demyelinating activity with antibody titre to the myelin/oligodendrocyte glycoprotein (MOG) J Neuroimmunol. 1987;17:61–69. doi: 10.1016/0165-5728(87)90031-2. [DOI] [PubMed] [Google Scholar]
  14. Linington C, Morgan BP, Scolding NJ, Wilkins P, Piddlesden S, Compston DA. The role of complement in the pathogenesis of experimental allergic encephalomyelitis. Brain. 1989;112:895–911. doi: 10.1093/brain/112.4.895. [DOI] [PubMed] [Google Scholar]
  15. Litzenburger T, Fassler R, Bauer J, Lassmann H, Linington C, Wekerle H, Iglesias A. B lymphocytes producing demyelinating autoantibodies: development and function in gene-targeted transgenic mice. J Exp Med. 1998;188:169–180. doi: 10.1084/jem.188.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lucchinetti C, Bruck W, Parisi J, Scheithauer B, Rodriguez M, Lassmann H. Heterogeneity of multiple sclerosis lesions: implications for the pathogenesis of demyelination [see comments] Ann Neurol. 2000;47:707–717. doi: 10.1002/1531-8249(200006)47:6<707::AID-ANA3>3.0.CO;2-Q. [DOI] [PubMed] [Google Scholar]
  17. Lucchinetti CF, Bruck W, Rodriguez M, Lassmann H. Distinct patterns of multiple sclerosis pathology indicates heterogeneity on pathogenesis. Brain Pathol. 1996;6:259–274. doi: 10.1111/j.1750-3639.1996.tb00854.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Mastaglia FL, Carroll WM, Jennings AR. Spinal cord lesions induced by antigalactocerebroside serum. Clin Exp Neurol. 1989;26:33–44. [PubMed] [Google Scholar]
  19. Matthews AE, Weiss SR, Shlomchik M, Hannum LG, Gombold J, Paterson Y. Antibody is required for clearance of infectious murine hepatitis virus A59 from the CNS but not the liver. J Immunol. 2001;167:5254–5263. doi: 10.4049/jimmunol.167.9.5254. [DOI] [PubMed] [Google Scholar]
  20. Miller DJ, Bright JJ, Sriram S, Rodriguez M. Successful treatment of established relapsing experimental autoimmune encephalomyelitis in mice with a monoclonal natural autoantibody. J Neuroimmunol. 1997;75:204–209. doi: 10.1016/S0165-5728(97)00027-1. [DOI] [PubMed] [Google Scholar]
  21. Miller DJ, Sanborn KS, Katzmann JA, Rodriguez M. Monoclonal autoantibodies promote central nervous system repair in an animal model of multiple sclerosis. J Neurosci. 1994;14:6230–6238. doi: 10.1523/JNEUROSCI.14-10-06230.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ozawa K, Saida T, Saida K, Nishitani H, Kameyama M. In vivo CNS demyelination mediated by antigalactocerebroside antibody. Acta Neuropathol. 1989;77:621–628. doi: 10.1007/BF00687890. [DOI] [PubMed] [Google Scholar]
  23. Pavelko KD, van Engelen BG, Rodriguez M. Acceleration in the rate of CNS remyelination in lysolecithin-induced demyelination. J Neurosci. 1998;18:2498–2505. doi: 10.1523/JNEUROSCI.18-07-02498.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Piddlesden SJ, Lassmann H, Zimprich F, Morgan BP, Linington C. The demyelinating potential of antibodies to myelin oligodendrocyte glycoprotein is related to their ability to fix complement. Am J Pathol. 1993;143:555–564. [PMC free article] [PubMed] [Google Scholar]
  25. Rodriguez M. Immunoglobulins stimulate central nervous system remyelination: electron microscopic and morphometric analysis of proliferating cells. Lab Invest. 1991;64:358–370. [PubMed] [Google Scholar]
  26. Schluesener HJ, Sobel RA, Linington C, Weiner HL. A monoclonal antibody against a myelin oligodendrocyte glycoprotein induces relapses and demyelination in central nervous system autoimmune disease. J Immunol. 1987;139:4016–4021. [PubMed] [Google Scholar]
  27. Sutherland RM, Chua MM, Lavi E, Weiss SR, Paterson Y. CD4+ and CD8+ T cells are not major effectors of mouse hepatitis virus A59-induced demyelinating disease. J Neuro Virol. 1997;3:225–228. doi: 10.3109/13550289709018297. [DOI] [PubMed] [Google Scholar]
  28. Talbot PJ, Buchmeier MJ. Catabolism of homologous murine monoclonal hybridoma IgG antibodies in mice. Immunology. 1987;60:485–489. [PMC free article] [PubMed] [Google Scholar]
  29. Van der Goes A, Kortekaas M, Hoekstra K, Dijkstra CD, Amor S. The role of anti-myelin (auto)-antibodies in the phagocytosis of myelin by macrophages. J Neuroimmunol. 1999;101:61–67. doi: 10.1016/S0165-5728(99)00133-2. [DOI] [PubMed] [Google Scholar]
  30. van Engelen BG, Miller DJ, Pavelko KD, Hommes OR, Rodriguez M. Promotion of remyelination by polyclonal immunoglobulin in Theiler’s virus-induced demyelination and in multiple sclerosis. J Neurol Neurosurg Psych. 1994;57:65–68. doi: 10.1136/jnnp.57.Suppl.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Wang FI, Stohlman SA, Fleming JO. Demyelination induced by murine hepatitis virus JHM strain (MHV-4) is immunologically mediated. J Neuroimmunol. 1990;30:31–41. doi: 10.1016/0165-5728(90)90050-W. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wu GF, Dandekar AA, Pewe L, Perlman S. CD4 and CD8 T cells have redundant but not identical roles in virus-induced demyelination. J Immunol. 2000;165:2278–2286. doi: 10.4049/jimmunol.165.4.2278. [DOI] [PubMed] [Google Scholar]
  33. Wu GF, Perlman S. Macrophage infiltration, but not apoptosis, is correlated with immune-mediated demyelination following murine infection with a neurotropic coronavirus. J Virol. 1999;73:8771–8780. doi: 10.1128/jvi.73.10.8771-8780.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Xue S, Sun N, Van Rooijen N, Perlman S. Depletion of blood-borne macrophages does not reduce demyelination in mice infected with a neurotropic coronavirus. J Virol. 1999;73:6327–6334. doi: 10.1128/jvi.73.8.6327-6334.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Neurovirology are provided here courtesy of Nature Publishing Group

RESOURCES