This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Lin, X.
Right arrow Articles by Rodriguez, M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Lin, X.
Right arrow Articles by Rodriguez, M.

 Previous Article  |  Next Article 

Journal of Virology, August 2002, p. 7799-7811, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7799-7811.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Transgenic Expression of Theiler's Murine Encephalomyelitis Virus Genes in H-2b Mice Inhibits Resistance to Virus-Induced Demyelination

Xiaoqi Lin,1 M. Kariuki Njenga,2 Aaron J. Johnson,3 Kevin D. Pavelko,3 Chella S. David,4 Larry R. Pease,4 and Moses Rodriguez3,4*

Department of Neurology, University of Chicago Medical Center, Chicago, Illinois 60637,1 Department of Neurology,3 Department of Immunology, Mayo Clinic and Foundation, Rochester, Minnesota 55905,4 Department of Veterinary PathoBiology, University of Minnesota, St. Paul, Minnesota 551082

Received 8 February 2002/ Accepted 22 April 2002

We investigated the role of the immune system in protecting against virus-induced demyelination by generating lines of transgenic B10 (H-2b) congenic mice expressing three independent contiguous coding regions of the Theiler's murine encephalomyelitis virus (TMEV) under the control of a class I major histocompatibility complex (MHC) promoter. TMEV infection of normally resistant B10 mice results in virus clearance and development of inflammatory demyelination in the spinal cord. Transgenic expression of the viral capsid genes resulted in inactivation of virus-specific CD8+ T lymphocytes (class I MHC immune function) directed against the relevant peptides, but it did not affect production of virus capsid-specific antibodies or lymphocyte proliferation to the virus antigen (class II MHC immune functions). Following intracerebral infection with TMEV, all three lines of mice survived the acute encephalitis but transgenic mice expressing VP1 (or the cluster of virus capsid proteins [VP4, VP2, and VP3] mapping to the left of VP1 in the TMEV genome) developed virus persistence and subsequent demyelination in spinal cord white matter. Transgenic mice expressing noncapsid proteins mapping to the right of VP1 (2A, 2B, 2C, 3A, 3B, 3C, and 3D) cleared the virus and did not develop demyelination. These results are consistent with the hypothesis that virus capsid gene products of TMEV stimulate class I-restricted CD8+ T-cell immune responses, which are important for virus clearance and for protection against myelin destruction. Presented within the context of self-antigens, inactivation of these cells by ubiquitous expression of relevant virus capsid peptides partially inhibited resistance to virus-induced demyelination.

* Corresponding author. Mailing address: Mayo Clinic and Foundation, 200 First St. Southwest, Rochester, MN 55905. Phone: (507) 284-4663. Fax: (507) 284-1637. E-mail: Rodriguez{at}mayo.edu.

Journal of Virology, August 2002, p. 7799-7811, Vol. 76, No. 15
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.15.7799-7811.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • Baida, G., Popko, B., Wollmann, R. L., Stavrou, S., Lin, W., Tretiakova, M., Krausz, T. N., Roos, R. P. (2008). A Subgenomic Segment of Theiler's Murine Encephalomyelitis Virus RNA Causes Demyelination. J. Virol. 82: 5879-5886 [Abstract] [Full Text]  
  • Myoung, J., Bahk, Y. Y., Kang, H. S., Dal Canto, M. C., Kim, B. S. (2008). Anticapsid Immunity Level, Not Viral Persistence Level, Correlates with the Progression of Theiler's Virus-Induced Demyelinating Disease in Viral P1-Transgenic Mice. J. Virol. 82: 5606-5617 [Abstract] [Full Text]  
  • Lin, X., Ma, X., Rodriguez, M., Roos, R. P. (2004). CD4+ T cells are important for clearance of DA strain of TMEV from the central nervous system of SJL/J mice. Int Immunol 16: 1237-1240 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»