Michel Brahic, M.D., Ph.D.
Consulting Professor

Ph.D. University of Provence, Marseilles, France, 1976.
M.D. University of Provence, Marseilles, France, 1968.
D307 Fairchild
299 Campus Drive
Stanford CA 94305-5124
Research Summary

Theiler’s virus, a neurotropic picornavirus, is a natural pathogen of mouse. It causes a persistent CNS infection with inflammation and demyelination which is model for multiple sclerosis. Following entry into the CNS, the virus infects neurons and is transported axonally. After a few weeks it disappears from neurons and persists only in glial cells, mainly oligodendrocytes, as well as in infiltrating macrophages. The Brahic laboratory found that mice with mutations in myelin genes were totally resistant to persistent infection. This lead the group to show that axon to myelin traffic of the virus is required for persistence (Roussarie et al. 2007, PloS Pathog. 3 :e23). Importantly this traffic takes place in the absence of axonal degeneration.

We are examining the mechanism of non-cytolytic axon to myelin traffic of this non-enveloped virus. We hypothesize that the virus makes use of a pre-existing mechanism of cytoplasmic exchange between axon and myelin. The existence of such exchanges has been suggested by ultra-structural studies but never functionally demonstrated. They could be essential for the role played by myelin in axon survival. We also investigate the reason for which the infection of myelin cytoplasmic channels appears to be essential for viral persistence. Could the virus escape immune detection in this highly specialized environment?

Copyright 2006 - 2010. The Laboratory of Karla Kirkegaard, Ph.D. All rights reserved.