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Marie Chow
Professor, Department of Microbiology & Immunology Virology Research Interest: Pathogenesis of picornavirus infections Ph.D ., Yale University Postdoctoral , Massachusetts Institute of Technology and Whitehead Institute for Biomedical Research Phone: (501) 686-5155 In our laboratory, we are interested in understanding the molecular basis of how picornaviruses cause disease. Picornaviruses are among the smallest of viruses, yet this virus family encompasses many of the major human viral pathogens, including poliovirus (paralytic poliomyelitis), hepatitis A virus (hepatitis), rhinoviruses (common cold) and coxsackie virus (hand, foot and mouth). These viruses are also among the simplest of viruses comprising of sixty copies of four capsid proteins (VP1, VP2, VP3 and VP4) which surround a single-strand of RNA of positive-sense. Like the other viruses of this family, the capsid proteins of poliovirus mediate many of the host interactions that are important determinants of disease pathology. They interact with specific receptors on the surface of susceptible cells, determining the host and tissue specificity of poliovirus. The proteins also protect the viral RNA genome from degradation, allowing the virus to enter and initiate primary infection in the gastro-intestinal tract. Finally, these proteins are also targets of the immune response that is induced by the host upon vaccination or infection and will protect the host upon reinfection. Because of these central roles, we are interested in understanding the relationship that capsid protein structure plays in determining the pathogenesis of poliomyelitis. Our studies most recently have concentrated on understanding how poliovirus enters the cell. We have identified that there are additional stages in the cell entry process that occur after the virus-receptor interaction and are presently identifying the relevant proteins and their roles in transporting the viral genome across the cell surface membrane. These studies involve the generation of site-specific mutants that are defective in the cell entry process and the development of new in vitro assays. Characterization of these mutants will allow us to study the biochemistry and cell biology of this pathway. We are also interested in understanding how the immune response protects against disease pathogenesis. Previously, we had identified the viral epitopes which are recognized by neutralizing antibodies. Most recently, we have identified the epitopes in the virus capsid that are recognized by poliovirus-specific T helper and T cytotoxic lymphocytes. Using transgenic mice which have incorporated the poliovirus receptor into its genome and are thus susceptible to poliovirus infection, we plan to study how these characterized responses from different branches of the immune system alter viral replication in the GI tract and central nervous system and interfere with migration of the virus from the GI tract to the CNS migration within the CNS. From these transgenic mice studies, we will understand in molecular terms the underlying basis of host protection by vaccines. References Wahid, R., Cannon, M.J., Chow, M. Virus-specific CD4+ and CD8+ cytotoxic T-cell responses and long-term T-cell memory in individuals vaccinated against polio. Wilkins, C., Dishough, R., Moore, S.C., Whitt, M.A., Chow, M. Machaca, K. RNA interference is an antiviral defence mechanism in Caenorhabditis elegans.
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