Comparative Medicine Program

Colin R. Parrish Back to Faculty Mentors

Research in the Parrish laboratory is directed to an understanding of the relationships between the genetic, evolutionary, and structural properties of animal viruses, their abilities to infect various animal species or their cultured cells, and the ability of the viruses to cause disease. Those studies involve a multidisciplinary approach. The system which has been studied most intensively is a group of closely related parvoviruses which infect and cause disease in several species of carnivores -- cats, dogs, mink, raccoons and their relatives. In addition to examining viruses isolated from the different species, the Parrish group has been analyzing site-directed mutants derived from various viruses. The objectives are to use genetic analysis of infectious DNA clones of the viruses to determine the effects of changes in the virus capsid proteins on the viral host range, antigenic structure, and on other properties of the virus such as its ability to bind sialic acid and to agglutinate erythrocytes. Dr. Parrish and his collaborators at Purdue University have solved the atomic structures of the capsids of both the canine and feline viruses, as well as of virus structures under varying conditions that might be encountered during cell infection. In addition, they are also examining the mechanisms of virus capsid assembly and disassembly using detailed site-directed mutagenesis and structural studies of contact regions between proteins. A second line of research is concerned with viruses in natural populations. Here the Parrish group has been using the parvovirus model to examine the evolution of viruses (both antigenic and sequence changes) during infection and spread through feral animal populations. They have shown that over 12 years there has been a series of step-wise changes in the viruses, with antigenic and genetic substitutions being observed world-wide on a number of occasions. Most recently they have initiated studies of the processes of cell entry by the viruses, using dominant-interfering mutants of mediators of endosomal trafficking and fusion, including dynamin, Rab5 and Rab7, as well as examining the processes of nuclear import. Research in which trainees could become involved include the continuation of the studies of parvoviruses and the cells they infect. The small size of the virus and its genome, and the results obtained so far, make this a powerful model system for examining relationships between the structure or genetics of viruses and their various expressed phenotypes. Trainees would gain experience with virtually all of the modern techniques which can be used in studies of infectious diseases and the agents that cause them. Recent Publications: Parrish, C.R. (1999) The host range and vari-ation of canine parvovirus, feline panleu-kopenia virus and mink enteritis virus. In: "Encyclopedia of Virology" 2nd Edition (Eds. Webster, R. G. and Granoff, A.) Barker, I.K., Parrish, C.R. Parvovirus infections of wild mammals. In: "Infectious Diseases of Wild Mammals" 2nd Edition, University of Iowa Press (in press). Parrish, C.R., Truyen, U. (1999) The evolution of parvoviruses. In: "Origin and Evolution of Viruses" (Eds. Domingo, E., Webster, R.G., Holland, J.J., Picknett, T.), Academic Press, London, 421-439. Wang, D., Parrish, C.R. (1999) hnRNP-related proteins binding near the 5'-end and within the genome of feline parvovirus can modify viral DNA replication. J. of Virology, 73: 7761-7768. Parker, J.S.L., Parrish, C.R. Cellular uptake and infection by canine parvovirus involves rapid dynamin-regulated clathrin-medicated endocytosis, followed by slower intracellular trafficking (Submitted to Journal of Virology).