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Journal of Virology, June 2008, p. 5519-5526, Vol. 82, No. 11
0022-538X/08/$08.00+0     doi:10.1128/JVI.01488-07
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Demyelinating and Nondemyelinating Strains of Mouse Hepatitis Virus Differ in Their Neural Cell Tropism

Jayasri Das Sarma,^1* Kathryn Iacono,^2, Lilli Gard,^2, Ryan Marek,¹ Lawrence C. Kenyon,³ Michael Koval,⁴ and Susan R. Weiss²

Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,¹ Department of Microbiology, University of Pennsylvania, Philadelphia, Pennsylvania 19104,² Department of Pathology, Anatomy and Cell Biology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107,³ Pulmonary, Allergy, and Critical Care Medicine Division, Department of Medicine, Emory University, Atlanta, Georgia 30322⁴

Received 6 July 2007/ Accepted 21 March 2008

Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is a correlation between the differential localization of viral antigen in spinal cord gray matter and that in white matter during acute infection and the ability to induce demyelination later on. Viral antigen from demyelinating strains is detected initially in both gray and white matter, with subsequent localization to white matter of the spinal cord, whereas viral antigen localization of nondemyelinating strains is restricted mainly to gray matter. This observation suggests that the localization of viral antigen to white matter during the acute stage of infection is essential for the induction of chronic demyelination. Overall, these observations suggest that isogenic demyelinating and nondemyelinating strains of MHV, differing in the spike protein expressed, infect neurons and glial cells in different proportions and that differential tropism to a particular CNS cell type may play a significant role in mediating the onset and mechanisms of demyelination.

Published ahead of print on 2 April 2008.

Present address: Medical Diagnostic Laboratories, L.L.C., Hamilton, NJ 08690.

Present address: University Medical Center Groningen, Department of Medical Microbiology, Virology Section; 9700 RB, Groningen, The Netherlands.

This article has been cited by other articles:

• Shindler, K. S., Kenyon, L. C., Dutt, M., Hingley, S. T., Sarma, J. D. (2008). Experimental Optic Neuritis Induced by a Demyelinating Strain of Mouse Hepatitis Virus. J. Virol. 82: 8882-8886 [Abstract] [Full Text]