Robert S. Fujinami

Professor of Pathology and
Adjunct Professor of Neurology

Robert Fujinami

B.A. University of Utah

Ph.D. Northwestern University

Research

References

robert.fujinami@hsc.utah.edu

Robert Fujinami's Lab Page

Robert Fujinami's PubMed Literature Search

 

Molecular BIology Program

Viral Pathogenesis / Autoimmunity

Research

Virus infection leading to central nervous system (CNS) demyelination

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). MS is often referred to as an immune mediated disease, where the body’s immune system is fooled into attacking myelin within the CNS. The cause of MS is not known. However, viral infections are often associated with the initiation and exacerbations of this disease. How different viruses trigger attacks of MS is still unclear, but at least two hypotheses have been put forth to explain how this could occur. The first hypothesis involves direct infection of the brain by a virus. This viral infection causes inflammation and damage to cells that produce myelin. This damage releases fragments of myelin that are recognized by autoreactive T cells which then are activated within the inflammatory milieu. These T cells that recognize epitopes of myelin proteins then trigger a series of events that result in more inflammation in the CNS and myelin destruction. A second hypothesis involves a virus infection taking place outside of the CNS where the immune response to the virus cross-reacts with CNS myelin or “self.” Therefore, T cells have the ability to recognize both the virus as well as myelin. These cells activated by the virus infection that also recognize myelin now ingress into the CNS and cause inflammation and demyelination. We are proposing to test a variation of this second hypothesis. We have evidence that the T cells that are activated following certain kinds of virus infections can recognize virus and myelin. We are proposing to explore how these cells are generated and understand how these T cells can recognize two disparate entities. In our preliminary studies, we find that the T cells that recognize both virus and self have more than one receptor on their surface. T cells normally have one T cell receptor (TCR) that recognizes just virus or self but not both; but, by having more than one receptor, the T cell can be activated by the TCR that recognizes virus and the other TCR targets myelin or self.

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 autoimmune 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.

Fujinami Figure

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

Selected Publications

  1. Cusick MF, Libbey JE, Doty DJ, DePaula-Silva AB, and Fujinami RS.  The Role of Peripheral Interleukin-6 in the Development of Seizures following Virus Encephalitis.  J NeuroVirol., 2017 doi: 10.1007/s13365-017-0554-8. [Epub ahead of print].  PMID:28741149.
  2. Patel DC, Wallis G, Dahle EJ, McElroy PB, Thomson KE, Tesi RJ, Szymkowski DE, West PJ, Smeal RM, Patel M, Fujinami RS, White HS, and Wilcox KS.  Hippocampal TNFa signaling contributes to seizure generation in an infection-induced mouse model of limbic epilepsy.  eNeuro, 4(2):e0105-17.2017, 2017.  PMID: 28497109.
  3. Soto R, Petersen C, Novis CL, Kubinak JL, Bell R, Stephens W.Z., Lane TE, Fujinami RS, Bosque A, O’Connell RM, and Round JL.  Microbiota promotes systemic T-cell survival through suppression of an apoptotic factor.  Proc Natl Acad Sci USA, 114(21):5497-5502, 2017.  PMID: 28487480.
  4. Libbey JE, Cusick MF, Doty DJ, and Fujinami RS.  Complement Components are Expressed by Infiltrating Macrophages/Activated Microglia Early Following Viral Infection.  Viral Immunol., 30(5):304-314, 2017.  PMID: 28402228.
  5. DePaula-Silva AB, Hanak TJ, Libbey JE, and Fujinami RS.  Theiler’s murine encephalomyelitis virus infection of SJL/J and C57BL/6J mice:  Models for multiple sclerosis and epilepsy.  J Neuroimmunol., 308:30-42, 2017.  PMID: 28237622.
  6. Libbey JE, and Fujinami RS.  Variable Genome Sequences of the Murine Pneumotropic Virus (Polyomaviridae) Regulatory Region Isolated from an Infected Mouse Tissue Viral Suspension.  Genome Announc., 4(3):e00405-e00416, 2016.  PMID: 27231357.
  7. Libbey JE, and Fujinami RS.  Complete Genome Sequence of Murine Pneumotropic Virus (Polyomaviridae) Clone pKV(37-1).  Genome Announc., 4(3):e00404-e00416, 2016.  PMID: 27198030.
  8. Libbey JE, Doty DJ, Sim JT, Cusick MF, Round JL, and Fujinami RS.  The effects of diet on the severity of central nervous system disease: one part of lab-to-lab variability.  Nutrition., 32:877-883, 2016.  PMID: 27133811.
  9. Libbey JE, Hanak TJ, Doty DJ, Wilcox KS, and Fujinami RS.  NBQX, a Highly Selective Competitive Antagonist of AMPA and KA Ionotropic Glutamate Receptors, Increases Seizures and Mortality Following Picornavirus Infection.  Exp. Neurol., 280:89-96, 2016.  PMCID: PMC4860063.
  10. Vezzani A, Fujinami RS, White HS, Preux PM, Blumcke I, Sander JW, and Loscher W.  Infections, Inflammation and Epilepsy.  Acta Neuropathol., 131(2):211-234, 2016.  PMCID: PMC4867498.

to page top

Last Updated: 8/11/17