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Journal of Virology, June 2005, p. 7113-7120, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7113-7120.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Viral Expression of CCL2 Is Sufficient To Induce Demyelination in RAG1^–/– Mice Infected with a Neurotropic Coronavirus

Taeg S. Kim¹ and Stanley Perlman^1,2*

Interdisciplinary Program in Immunology,¹ Departments of Pediatrics and Microbiology, University of Iowa, Iowa City, Iowa 52242²

Received 10 December 2004/ Accepted 19 January 2005

Mouse hepatitis virus strain JHM causes a chronic demyelinating disease in susceptible strains of rodents. Demyelination does not develop in infected RAG1^–/– (recombination activation gene-deficient) mice but can be induced by several experimental interventions, including adoptive transfer of virus-specific T cells or antibodies. A common feature of demyelination in these models is extensive infiltration of macrophages/microglia into the white matter. The data obtained thus far do not indicate whether macrophage/microglia infiltration, in the absence of T cells or antibody, is sufficient to mediate demyelination. To determine whether the expression of a single macrophage chemoattractant, in the context of virus infection, could initiate the demyelinating process, we engineered a recombinant coronavirus that expressed the chemokine CCL2/monocyte chemoattractant protein-1. CCL2 has been implicated in macrophage infiltration into the central nervous system and is involved in demyelination in many experimental models of demyelination. Extensive macrophage/microglia infiltration and demyelination has developed in RAG1^–/– mice infected with this recombinant virus. Thus, these results suggest that the minimal requirement for demyelination is increased expression of a single macrophage-attracting chemokine in the context of an inflammatory milieu, such as that induced by a viral infection.

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

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Journal of Virology, June 2005, p. 7113-7120, Vol. 79, No. 11
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.11.7113-7120.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

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