Abstract
Infection of mice with the coronavirus mouse hepatitis virus induces primary demyelination in susceptible strains of rodents. Although demyelination is the primary pathological process detected in the central nervous system of infected mice, axonal dysfunction and damage also occur concomitantly with demyelination. This process is T cell mediated, with either CD4 or CDS T cells sufficient for MHV-induced axonal damage. A striking feature is that axonal damage occurs early in the disease process, at nearly the same time as demyelination is first observed. Axonal damage in MHV-infected mice has many similarities with the parallel process in humans with multiple sclerosis.
Chapter PDF
Similar content being viewed by others
References
Noseworthy JH. Progress in determining the causes and treatment of multiple sclerosis. Nature. 1999;399:A40–A47.
Hemmer B, Archelos JJ, Hartung HP. New concepts in the immunopathogenesis of multiple sclerosis. Nat Rev Neurosci. 2002;3:291–301.
Lassmann H. The pathology of multiple sclerosis and its evolution. Philos Trans R Soc Lond B Biol Sci. 1999;354:1635–40.
De Stefano N, Matthews PM, Narayanan S, Francis GS, Antel JP, Arnold DL. Axonal dysfunction and disability in a relapse of multiple sclerosis: longitudinal study of a patient. Neurology. 1997;49:1138–41.
Trapp B, Peterson J, Ransohoff R, Rudick R, Monk S, Bo L. Axonal transection in the lesions of multiple sclerosis. New Engl. J. Med. 1998;338:278–285.
Ferguson B, Matyszak M, Esiri M, Perry V. Axonal damage in acute multiple sclerosis lesions. Brain. 1997; 120:393–399.
Matthews PM, De Stefano N, Narayanan S, et al. Putting magnetic resonance spectroscopy studies in context: axonal damage and disability in multiple sclerosis. Sem. Neurol. 1998; 18:327–36.
Brex PA, Ciccarelli O, O’Riordan JI, Sailer M, Thompson AJ, Miller DH. A longitudinal study of abnormalities on MRI and disability from multiple sclerosis. N Engl J Med. 2002;346:158–64.
Waxman SG. Demyelinating diseases-new pathological insights, new therapeutic targets. N Engl J Med. 1998;338:323–5.
Kornek B, Storch MK, Weissert R, et al. Multiple sclerosis and chronic autoimmune encephalomyelitis: a comparative quantitative study of axonal injury in active, inactive, and remyelinated lesions. Am J Pathol. 2000;157(1):267–76.
Raine CS, Cross AH. Axonal dystrophy as a consequence of long-term demyelination. Lab. Invest. 1989;60:714–725.
Sathornsumetee S, McGavern DB, Ure DR, Rodriguez M. Quantitative ultrastructural analysis of a single spinal cord demyelinated lesion predicts total lesion load, axonal loss, and neurological dysfunction in a murine model of multiple sclerosis. Am J Pathol. 2000;157(4): 1365–76.
Dandekar AA, Wu G, Pewe LL, Perlman S. Axonal damage is T cell mediated and occurs concomitantly with demyelination in mice infected with a neurotropic cornavirus. J. Virol. 2001;75:6115–6120.
Stohlman SA, Bergmann CC, Perlman S. Mouse hepatitis virus. In: Ahmed R, Chen I, eds. Persistent Viral Infections. New York: John Wiley & Sons, Ltd.; 1998:537–557.
Haring J, Perlman S. Mouse hepatitis virus. Curr Opin Microbiol. 2001;4:462–6.
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.
Mombaerts P, Iacomini J, Johnson RS, Herrup K, Tonegawa S, Papaloannou VE. RAG-1-deficient mice have no mature B and T lymphocytes. Cell. 1992;68:869–877.
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.
Pasick J, Kalicharran K, Dales S. Distribution and trafficking of JHM coronavirus structural proteins and virions in primary neurons and the OBL-21 neuronal cell line. J. Virol. 1994;68:2915–2928.
Pewe L, Haring J, Perlman S. CD4 T-cell-mediated demyelination is increased in the absence of gamma interferon in mice infected with mouse hepatitis virus. J Virol. 2002;76:7329–33.
Pewe LL, Perlman S. CD8 T cell-mediated demyelination is IFN-γ dependent in mice infected with a neurotropic coronavirus. J. Immunol.2002; 168:1547–1551.
Kirkpatrick LL, Brady ST. Modulation of the axonal microtubule cytoskeleton by myelinating Schwann cells. J Neurosci. 1994; 14:7440–50.
Boison D, Stoffel W. Disruption of the compacted myelin sheath of axons of the central nervous system in proteolipid protein-deficient mice. Proc Natl Acad Sci U S A. 1994;91:11709–13.
Griffiths I, Klugmann M, Anderson T, et al. Axonal swellings and degeneration in mice lacking the major proteolipid of myelin. Science.1998;280:1610–1613.
Rivera-Quinones C, McGavern D, Schmelzer J, Hunter S, Low P, Rodriguez M. Absence of neurological deficits following extensive demyelination in a class I-deficient murine model of multiple sclerosis. Nature Med, 1998;4:187–193.
Felts PA, Baker TA, Smith KJ. Conduction in segmentally demyelinated mammalian central axons. J Neurosci. 1997;17:7267–77.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2005 Springer Science+Business Media, Inc.
About this chapter
Cite this chapter
Dandekar, A.A., Perlman, S. (2005). Axons and Neurons in Corona Virus-Induced Demyelination. In: Lavi, E., Constantinescu, C.S. (eds) Experimental Models of Multiple Sclerosis. Springer, Boston, MA. https://doi.org/10.1007/0-387-25518-4_39
Download citation
DOI: https://doi.org/10.1007/0-387-25518-4_39
Publisher Name: Springer, Boston, MA
Print ISBN: 978-0-387-25517-0
Online ISBN: 978-0-387-25518-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)