We are interested in the mechanisms involved in immune-mediated demyelination following infection with Theiler’s virus as a model system for human multiple sclerosis. Using many fusion proteins as well as synthetic peptides containing various parts of Theiler's viral coat proteins, we have mapped the areas recognized by antibodies, helper T cells and cytotoxic T cells from susceptible and resistant mice infected with Theiler’s virus. The potential role of individual viral antigens and the immune cell types in the pathogenesis of demyelination is investigated, including the type of T cell responses in the periphery and the central nervous system, as well as the cytokines and chemokines involved. Several low-pathogenic mutant viruses have been isolated and characterized to better understand the pathogenic mechanisms. In addition, several recombinant viruses modified in the immune recognition sites and transgenic mice expressing viral antigens and consequently tolerant to immune responses to the virus have been generated. In addition, transgenic mice expressing T cell receptors specific for viral determinants have also been generated recently.
Using these recombinant viruses and transgenic mice, we are currently analyzing the types of immune responses involved in the pathogenesis (and/or the protection), the potential role of T cells specific for different viral proteins and their T cell receptor repertoire specific for viral determinants during viral infection and steps involved in the initiation of pathogenic inflammation. In particular, the initiation of inflammatory responses by resident cells in the brain upon viral infection leading to demyelination is being investigated and these include the signaling mechanisms involved in the activation of various cytokine and chemokine gene expression induced by viral infection.
Publications:
Kang, B.-S., Lyman, M. L., and Kim, B. S. The majority of infiltrating CD8+ T cells in the CNS of susceptible SJL/J mice infected with Theiler’s encephalomyelitis virus are virus-specific and fully functional. Journal of Virology. 76:6577-6585. 2002.
Palma, J. P., Kwon, D.-H., Clipstone, N., and Kim, B. S.: Induction of proinflammatory cytokines in primary glial cell cultures infected with Theiler’s virus requires NFkB activation. Journal of Virology 77:6322-6331, 2003.
Kwon, D.-H., Fuller, A. C., Palma, J. P., Choi, I.-H., and Kim, B. S.: Induction of chemokines in human astrocytes by picornavirus infection requires activation of both AP-1 and NFkB. Glia 45:287-296, 2004.
