Robert S. Fujinami
Professor of Neurology and of Pathology
B.A. University of Utah
Ph.D. Northwestern University
Bob Fujimani's PubMed Literature Search
Research
Virus infection leading to central nervous system (CNS) demyelination. Theiler’s virus causes an encephalomyelitis in mice and this infection mimics multiple sclerosis (MS) in humans. The virus spreads through the CNS and infects white matter particularly the oligodendrocytes and astrocytes. This project involves 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, MS. These data were generated using viruses encoding myelin basic protein, and myelin proteolipid protein. Other viral constructs coding for other CNS proteins need to be characterized. This project involves definition of how these viral constructs can modulate immune responses and whether infection leads to autoimmune disease.
Virus Infection and Epilepsy. We have created a new infectious agent model for temporal lobe epilepsy. In our previous studies, SJL/J mice infected with Theiler’s murine encephalomyelitis virus (TMEV) develop a persistent viral infection with an inflammatory demyelinating pathology in the CNS. In recent studies, C57BL/6 mice infected with TMEV develop acute seizures that resolve and later have spontaneous seizures. TMEV in C57BL/6 mice targets the hippocampus. The ensuing acute innate inflammatory response contributes to the acute seizures. We are investigating the contributions of the innate immune response to the acquisition of seizures.
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. Libbey JE, Fujinami RS (2009) Potential triggers of MS. In Molecular Basis of Multiple Sclerosis. The Immune System. Series: Results and Problems in Cell Differentiation. R Martin, A Lutterotti (Eds.), Springer-Verlag, Berlin, epub January 8, 2009
2. Tsunoda I, Tanaka T, Taniguchi M, Fujinami RS (2009) Contrasting roles for Va14+ NKT cells in a viral model for multiple sclerosis. J NeuroVirol 15(1):90-8
3. Tsunoda I, Libbey JE, Fujinami RS (2009) Theiler’s murine encephalomyelitis virus attachment to the gastrointestinal tract is associated with sialic acid binding. J NeuroVirol 15(1):81-9
4. Theil DJ, Libbey JE, Rodriguez F, Whitton JL, Tsunoda I, Derfuss TJ, Fujinami RS (2008) Targeting myelin proteolipid protein to the MHC class I pathway by ubiquitination modulates the course of experimental allergic encephalomyelitis. J Neuroimmunol 204:92-100
5. Tsunoda I, Tanaka T, Fujinami RS (2008) Regulatory role of CD1d in neurotropic virus infection. J Virol 82(20):10279-89
6. 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 85(1):28-39
7. Peterson LK, Tsunoda I, Fujinami RS (2008) Role of CD5+ B-1 cells in EAE pathogenesis. Autoimmunity 41(5):353-62
8. Libbey JE, Kirkman NJ, Smith MCP, Tanaka T, Wilcox KS, White HS, Fujinami RS (2008) Seizures following picornavirus infection. Epilepsia 49(6):1066-74
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
