5 postdoctoral fellows, 6 graduate students
Our research program uses x-ray crystallographic methods to determine the structures of polio and related small icosahedral viruses at near atomic resolution. Although these viruses have relatively few components (consisting of a protein coat and a small RNA genome), they must perform a variety of biological functions at various stages of their replicative cycles. These viruses thus provide and excellent model for studying the correlation of structure with biological function and for gaining insight into the principles that govern macromolecular structure, assembly and disassembly, immune recognition, and viral pathogenesis. Immediate practical applications include vaccine development and antiviral drug design. Over the past several years, we have solved the structure of several viruses, included several strains of poliovirus and Theiler's virus, a murine cardiovirus which is considered to be a model for viral-induced demyelinating diseases. Current projects include structural studies of assembly and cell-entry intermediates of poliovirus, mutant and chimeric poliovirus with altered biological properties, and complexes of poliovirus with antiviral drugs. In addition, we have recently initiated a program of structural studies of virus-related proteins including the poliovirus protease/replicase precursor and its compelxes with RNA, the poliovirus receptor, the core herpes virus, and essential enzymes from herpes simplex and cytomegalovirus.
Hogle, J. M., M. Chow, and D. J. Filman. 1985. Three-dimensional structure of poliovirus at 2.9 A resolution. Science 229:1358-1365.
Fricks, C. E. and J. M. Hogle. 1990. Cell-induced conformational change of poliovirus: Externalization of the amino terminus of VP1 is responsible for liposome binding. J. Virol. 64:1934-1945.
Grant, R. A., D. J. Filman, R. S. Fujinami, J. P. Icenogle, and J. M. Hogle. 1992. Three-dimensional structure of Theiler virus. Proc. Natl. Acad. Sci. USA 89:2061-2065.
Grant, R. A., C. Hiremath, D. J. Filman, R. Syed, K. Andries, and J. M. Hogle. 1994. Structures of poliovirus complexes with antiviral drugs: implications for viral stability and drug design. Curr. Biol. 4:784-797.
Basavappa, R., R. Syed, O. Flore, J. P. Icenogle, D. J. Filman, and J. M. Hogle. 1994. Role and mechanism of the maturation cleavage of VP0 in poliovirus assembly: Structure of the empty capsid assembly intermediate at 2.9Å resolution. Protein Science 3:1651-1669.
Wien, M.W., M. Chow, J.M. Hogle (1996). Poliovirus: new insights from an old paradigm. Structure 4:763-767.