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Journal of Virology, October 2008, p. 10279-10289, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00734-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Regulatory Role of CD1d in Neurotropic Virus Infection{triangledown}

Ikuo Tsunoda,* Tomoko Tanaka, and Robert S. Fujinami

Department of Pathology, Division of Cell Biology & Immunology, University of Utah School of Medicine, 30 North 1900 East, Salt Lake City, Utah 84132-2305

Received 3 April 2008/ Accepted 29 July 2008

The GDVII strain of Theiler's murine encephalomyelitis virus (TMEV) causes an acute fatal polioencephalomyelitis in mice. Infection of susceptible mice with the DA strain of TMEV results in an acute polioencephalomyelitis followed by chronic immune-mediated demyelination with virus persistence in the central nervous system (CNS); DA virus infection is used as an animal model for multiple sclerosis. CD1d-restricted natural killer T (NKT) cells can contribute to viral clearance and regulation of autoimmune responses. To investigate the role of CD1d in TMEV infection, we first infected CD1d-deficient mice (CD1–/–) and wild-type BALB/c mice with GDVII virus. Wild-type mice were more resistant to virus than CD1–/– mice (50% lethal dose titers: wild-type mice, 10 PFU; CD1–/– mice, 1.6 PFU). Wild-type mice had fewer viral antigen-positive cells with greater inflammation in the CNS than CD1–/– mice. Second, an analysis of DA virus infection in CD1–/– mice was conducted. Although both wild-type and CD1–/– mice had similar clinical signs during the first 2 weeks after infection, CD1–/– mice had an increase in neurological deficits over those observed in wild-type mice at 3 to 5 weeks after infection. Although wild-type mice had no demyelination, 20 and 60% of CD1–/– mice developed demyelination at 3 and 5 weeks after infection, respectively. TMEV-specific lymphoproliferative responses, interleukin-4 (IL-4) production, and IL-4/gamma interferon ratios were higher in CD1–/– mice than in wild-type mice. Thus, CD1d-restricted NKT cells may play a protective role in TMEV-induced neurological disease by alteration of the cytokine profile and virus-specific immune responses.

* Corresponding author. Mailing address: Department of Pathology, Division of Cell Biology & Immunology, University of Utah School of Medicine, 30 North 1900 East, MREB, Room 218, Salt Lake City, UT 84132. Phone: (801) 581-4407. Fax: (801) 585-3311. E-mail: ikuo.tsunoda{at}hsc.utah.edu

{triangledown} Published ahead of print on 6 August 2008.

Journal of Virology, October 2008, p. 10279-10289, Vol. 82, No. 20
0022-538X/08/$08.00+0     doi:10.1128/JVI.00734-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.





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