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Journal of Virology, November 2007, p. 11690-11702, Vol. 81, No. 21
0022-538X/07/$08.00+0 doi:10.1128/JVI.01034-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Min H. Kang,
Alyson C. Fuller,
Bongsu Kang,
Daniel Gallo, and
Byung S. Kim*
Department of Microbiology and Immunology and Institute for Neuroscience, Northwestern University Feinberg Medical School, 303 East Chicago Ave., Chicago, Illinois 60611
Received 11 May 2007/ Accepted 13 August 2007
Infection with Theiler's murine encephalomyelitis virus (TMEV) in the central nervous system (CNS) causes an immune system-mediated demyelinating disease similar to human multiple sclerosis in susceptible but not resistant strains of mice. To understand the underlying mechanisms of differential susceptibility, we analyzed viral replication, cytokine production, and costimulatory molecule expression levels in microglia and macrophages in the CNS of virus-infected resistant C57BL/6 (B6) and susceptible SJL/J (SJL) mice. Our results indicated that message levels of TMEV, tumor necrosis factor alpha, beta interferon, and interleukin-6 were consistently higher in microglia from virus-infected SJL mice than in those from B6 mice. However, the levels of costimulatory molecule expression, as well as the ability to stimulate allogeneic T cells, were significantly lower in TMEV-infected SJL mice than in B6 mice. In addition, microglia from uninfected naïve mice displayed differential viral replication, T-cell stimulation, and cytokine production, similar to those of microglia from infected mice. These results strongly suggest that different levels of intrinsic susceptibility to TMEV infection, cytokine production, and T-cell activation ability by microglia contribute to the levels of viral persistence and antiviral T-cell responses in the CNS, which are critical for the differential susceptibility to TMEV-induced demyelinating disease between SJL and B6 mice.
Published ahead of print on 22 August 2007.
Present address: Credit Suisse, Eleven Madison Avenue, New York, NY 10010.
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