The Challenges of, and Responses to, Viral Infections in the Central Nervous System
Wednesday, October 13, 2004
Organizer: Carol S. Reiss, New York University
This highly interdisciplinary group brings together immunologists and neuroscientists interested in exploring the intersection of these two fields in periodic meetings that include discussions of basic, clinical, and translational aspects of this emerging field.
Presentations:
5:00–7:30
Glenn Rall, Fox Chase Cancer Center, "Measles Virus Spread in Neurons and the Surprising Connection to Neuropathogenesis."
Stanley Perlman, University of Iowa, "Immunopathogenesis of Coronavirus-Induced Demyelination."
Christine Biron, Department of Molecular Microbiology and Immunology, Division of Biology and Medicine, Brown University, "Innate Immune Responses to Viral Infections: Regulating Cytokine Functions to Shape Systemic Responses."
Abstracts
"Measles Virus Spread in Neurons and the Surprising Connection to Neuropathogenesis"
Glenn Rall
We have extensively characterized measles virus (MV) replication, spread, and pathogenesis in the central nervous system (CNS) of a novel transgenic mouse model. These mice express human CD46, one of the MV receptors, exclusively targeted to CNS neurons. Unrestricted MV spread occurs in CD46+ immunocompromised mice, which go on to develop severe CNS illness, characterized by tremors, weight loss, and paralysis. Interestingly, neuronal death and syncytia formation are not observed in these animals or in infected primary hippocampal neurons derived from embryonic transgenic mice. This suggested that the pathogenesis of MV infection in immunologically compromised mice was more likely due to neuronal dysfunction than to neuronal death. We have recently shown that the transsynaptic spread adopted by MV upon neuronal entry may account for this nonlytic pathogenesis, perhaps by engagement of important neurotransmitter receptors at the synapse.
"Immunopathogenesis of Coronavirus-Induced Demyelination"
Stanley Perlman
Mouse hepatitis virus (MHV), a member of the coronavirus family, causes neurological diseases that have similarities to the human disease multiple sclerosis. A hallmark of the murine infection with MHV is the development of demyelination. In these animals, myelin destruction is almost completely immune mediated. Either antivirus T cells or antivirus antibodies can mediate demyelination. Further, individual subsets of T cells mediate demyelination in the absence of the other, although the course of disease is remarkably different. Another factor adding to the complexity of the demyelinating process is the ability of the coronavirus to mutate. Mutations that make the virus more virulent and others that effect viral evasion of the immune response have been identified and change the pathogenesis of the infection. Of note, MHV is related to the coronavirus that causes the severe acute respiratory syndrome (SARS) and causes pathological changes in mice with some similarity to those observed in patients with SARS.
"Innate Immune Responses to Viral Infections: Regulating Cytokine Functions to Shape Systemic Responses"
Christine Biron
Innate cytokines are important regulators of antimicrobial defense and immune responses. They can act globally to communicate conditions and needs, and certain of these can interact with the neuroendocrine system to induce hormonal responses for feedback regulation. This laboratory is studying the induction and function of innate cytokines during viral infections. In particular, mouse responses to challenges with lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV) are being contrasted. This work is advancing understanding of the fine-tuning of endogenous cytokine responses to infection and of the importance of linking immune and neuroendocrine systems for the protection of the host. This wo