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. Libbey JE, Peterson LK, Tsunoda I, Fujinami RS (2006) Monoclonal MOG-reactive autoantibody from progressive EAE has the characteristics of a natural antibody. J. Neuroimmunol. 173(1-2):135-45
2. Tsunoda I, Libbey JE, Kobayashi-Warren M, Fujinami RS (2006) IFN-g production and astrocyte killing by autoreactive T cells induced by Theiler’s virus infection: Role of viral strains and capsid proteins. J. Neuroimmunol. 172(1-2):85-93
3. McCoy L, Tsunoda I, Fujinami RS (2006) Multiple sclerosis and virus induced immune responses: Autoimmunity can be primed by molecular mimicry and augmented by bystander activation. Autoimmunity 39(1):9-19
4. Fujinami RS, von Herrath MG, Christen U, Whitton JL (2006) Molecular mimicry, bystander activation or viral persistence: Infections and autoimmune disease. Clin. Microbiol. Rev. 19(1):80-94
5. Tsunoda I, Libbey JE, Kuang L-Q, Terry EJ, Fujinami RS (2005) Massive apoptosis in lymphoid organs is animal models for primary and secondary progressive multiple sclerosis. Am. J. Pathol. 167(6):1631-46
6. Libbey JE, Sweeten TL, McMahon WM, Fujinami RS (2005) Autistic disorder and viral infections. J. NeuroVirol. 11(1):1-10
7. Tsunoda I, Kuang L-Q, Igenge IZM, Fujinami RS (2005) Converting relapsing remitting to secondary progressive experimental allergic encephalomyelitis (EAE) by ultraviolet B irradiation. J. Neuroimmunol. 160(1-2):122-134
8. Tsunoda I, Lane TE, Blackett J, Fujinami RS (2004) Distinct roles for IP-10/CXCL10 in three animal models, Theiler's virus infection, EAE, and MHV infection, for multiple sclerosis: implications of differing roles for IP-10 among the subtypes of multiple sclerosis. Mult. Scler. 10(1):26-34
9. Von Herrath MG, Fujinami RS, Whitton JL (2003) Microorganisms and autoimmunity: making the barren field fertile? Nat. Rev. Microbiol. 1(2):151-157
10. Fujinami RS, Sweeten TL (2003) Letting antibodies get to your head. Nat. Med. 9(7):823-825
11. Wang M, Howell J, Libbey JE, Tainer JA, Fujinami RS (2003) Manganese Superoxide Dismutase Induction during Measles Virus Infection. J. Med. Virol. 70(3):470-474
12. Tsunoda I, Kuang L-Q, Libbey JE, Fujinami RS (2003) Axonal Injury Heralds Virus Induced Demyelination. Am. J. Pathol. 162(4):1259-1269
13. Wang M, Libbey JE, Tsunoda I, Fujinami RS (2003) Modulation of Immune System Function by Measles Virus Infection. II. Infection of B Cells Leads to the Production of a Soluble Factor that Arrests Uninfected B Cells in G0/G1. Viral Immunol. 16(1):45-56
