Robert S. Fujinami
Professor of Neurology and of Pathology
B.A. University of Utah
Ph.D. Northwestern University
Research
Virus infection leading to central nervous system (CNS) demyelination. Theiler's virus causes an encephalomyelitis in mice. This infection mimics multiple sclerosis in humans. The virus spreads through the CNS and infects white matter particularly the oligodendrocytes and astrocytes. This potential project will involve understanding the virologic and immunologic participation in this CNS demyelinating disease.
How virus infection modulates immune responses leading to autoimmune disease. Genetically altered viruses encoding myelin proteins can either protect against or enhance an autoimmune disease known as experimental allergic encephalomyelitis (EAE). This is a model for the human disease, multiple sclerosis. These data were generated using viruses encoding myelin basic protein, and myelin proteolipid protein. Other viral constructs coding for other central nervous system proteins need to be characterized. This project will involve definition of how these viral constructs can modulate immune responses and whether infection leads to autoimmune disease.
Progressive versus relapsing-remitting autoimmune disease. Different forms of MS are also being investigated. MS can be divided into four clinical forms: relapsing-remitting (RR), primary progressive (PP), secondary progressive (SP) and progressive relapsing (PR). The pathogenesis of the progressive forms of MS remains unclear, partly due to the lack of animal models that have these clinical patterns of disease.
Immunologic basis for autism. We are investigating the etiology and pathogenesis of autism. This developmental disease is acknowledged as a syndrome having a broad range of symptoms. It appears that genetics play a major role in the development of this disease, but environmental factors may also contribute to the disease. We are investigating immune responses to microbes and central nervous system components in autistic patients.
Photomicrograph of Theiler's virus-infected cell. Note the crystalline array of the viral particles in the cytoplasm of the cell. Virus causes a persistent infection of the central nervous system
References
1. Peterson LK, Masaki T, Wheelwright SR, Tsunoda I, Fujinami RS (2008) Cross-reactive myelin antibody induces renal pathology. Autoimmunity, In Press
2. Peterson LK, Tsunoda I, Libbey JE, Fujinami RS (2008) Role of B:T cell ratio in suppression of clinical signs: A model for silent MS. Exp. Mol. Path., In Press
3. Libbey JE, Smith MCP, Tanaka T, Kirkman NJ, Wilcox KS, White HS, Fujinami RS (2008) Seizures following picornavirus infection. Epilepsia (epub ahead of print)
4. Peterson LK, Tsunoda I, Fujinami RS (2008) Role of CD5+ B-1 cells in EAE pathogenesis. Autoimmunity, In Press
5. Libbey JE, Coon HH, Kirkman NJ, Sweeten TL, Miller JN, Stevenson EK, Lainhart JE, McMahon WM, Fujinami RS (2008) Are there enhanced MBP autoantibodies in autism? J Autism Dev Disord 38:324-32
6. Kirkman NJ*, Libbey JE*, Sweeten TL, Coon HH, Miller JN, Stevenson EK, Lainhart JE, McMahon WM, Fujinami RS (2008) How relevant are GFAP autoantibodies in autism and Tourette syndrome? J Autism Dev Disord 38:333-41 (*equal contribution)
7. Fujinami RS, Oldstone MBA (2008) Immunopathology of virus infection. In Encyclopedia of Virology, Third Edition, B Mahy, MHV van Regenmortel (Eds.), Elsevier Oxford, UK
8. Tsunoda I, Tanaka T, Saijoh Y, Fujinami RS (2007) Targeting inflammatory demyelinating lesions to sites of Wallerian degeneration. Am J Pathol 171:1563-75
9. Tsunoda I, Libbey JE, Fujinami RS (2007) Sequential polymicrobial infections lead to CNS inflammatory disease: Possible involvement of bystander activation in heterologous immunity. J Neuroimmunol 188:22-33
10. Tsunoda I, Libbey JE, Fujinami RS (2007) TGF-β1 suppresses T cell infiltration and VP2 puff B mutation enhances apoptosis in acute polioencephalitis induced by Theiler’s virus. J Neuroimmunol 190:80-9
