Re-emerging Infections of the CNS
Wednesday, December 14, 2005
Presented by the Brain Dysfunction and Neuroimmunology Discussion Group
Organizers: Carol Shoshkes Reiss, New York University School of Medicine; Mady Hornig, Columbia University
The Neuroimmunology Discussion Group focuses on the interface between the immune system and the nervous system both in the brain and in the periphery, in normal and pathological conditions. This highly interdisciplinary group seeks to bring together immunologists and neuroscientists interested in exploring the intersection of these two fields in periodic meetings that will include discussions of basic, clinical and translational aspects of this emerging field.
5:00 -7:00: Presentations
Eckard Wimmer, Stony Brook University, "Studies of Poliovirus Pathogenesis Leading to Flaccid Paralysis."
Kenneth Tyler, University of Colorado Health Science Center, "Progressive Multifocal Leukoencephalopathy (PML)."
"Studies of Poliovirus Pathogenesis Leading to Flaccid Paralysis"
Poliovirus (PV), a human enterovirus, is a neurotropic virus by mistake. It replicates to high titers in the GI tract, causing little or no complications. Only rarely, at a rate of 10-2 to 10–3, does PV invade the CNS to target and destroy predominantly motor neurons. A key determinant of PV infection is the cellular receptor CD155, a glycoprotein that is abundantly expressed in the GI tract and in cells of the GALT. Surprisingly, the precise nature of cells in the GI tract supporting PV replication is as yet unknown. Recent studies have indicated that CD155 is actively involved in PV retrograde axonal transport to neurons, a mechanism that will be discussed. PV pathogenesis, however, is determined by multiple parameters as, for example, genome mutations attenuating neurovirulence. A new genomic locus of PV attenuation will be presented.
"Progressive Multifocal Leukoencephalopathy (PML)"
PML is an opportunistic infection of the central nervous system (CNS) characterized by demyelination resulting from reactivation and subsequent lytic infection of oligodendrocytes by JC polyomavirus. PML is a major opportunistic infection in patients with impaired cell-mediated immunity including those with AIDS, organ transplants, lymphoproliferative disorders and leukemia. New attention has been focused on PML and its pathogenesis as a result of reports of the surprising and unexpected occurrence of PML in two patients with MS and one patient with Crohn's disease who were treated with natalizumab, a humanized monoclonal antibody against alpha4 integrins. PML had not previously been associated with either MS or inflammatory bowel disease. The molecular biology, pathogenesis and immunology of JCV infection; the clinical and laboratory features of PML, and the options for treatment of this devastating disease, will be reviewed. The potential mechanisms by which natalizumab treatment may have led to the development of PML and strategies for identifying patients at risk for developing disease will be discussed.