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Journal of Virology, July 2001, p. 6115-6120, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6115-6120.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

Axonal Damage Is T Cell Mediated and Occurs Concomitantly with Demyelination in Mice Infected with a Neurotropic Coronavirus

Ajai A. Dandekar,1 Gregory F. Wu,2 Lecia Pewe,3 and Stanley Perlman1,2,3,4,*

Interdisciplinary Programs in Immunology1 and Neuroscience2 and Departments of Pediatrics3 and Microbiology,4 University of Iowa, Iowa City, Iowa 52242

Received 10 January 2001/Accepted 28 March 2001

Mice infected with mouse hepatitis virus (MHV) strain JHM develop primary demyelination. Herein we show that axonal damage occurred in areas of demyelination and also in adjacent areas devoid of myelin damage. Immunodeficient MHV-infected RAG1-/- mice (mice defective in recombinase activating gene 1 expression) do not develop demyelination unless they receive splenocytes from a mouse previously immunized against MHV (G. F. Wu, A. Dandekar, L. Pewe, and S. Perlman, J. Immunol. 165:2278-2286, 2000). In the present study, we show that adoptive transfer of T cells was also required for the majority of the axonal injury observed in these animals. Both demyelination and axonal damage were apparent by 7 days posttransfer. Recent data suggest that axonal injury is a major factor in the long-term disability observed in patients with multiple sclerosis. Our data demonstrate that immune system-mediated damage to axons is also a common feature in mice with MHV-induced demyelination. Remarkably, there appeared to be a minimal, if any, interval of time between the appearance of demyelination and that of axonal injury.

* Corresponding author. Mailing address: Department of Pediatrics, 2042 Medical Laboratories, University of Iowa, Iowa City, IA 52242. Phone: (319) 335-8549. Fax: (319) 335-8991. E-mail: Stanley-Perlman{at}uiowa.edu.

Journal of Virology, July 2001, p. 6115-6120, Vol. 75, No. 13
0022-538X/01/$04.00+0   DOI: 10.1128/JVI.75.13.6115-6120.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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