Our long-term objective is to aid in the development of new diagnostic and therapeutic approaches to herpesvirus related diseases of man. We plan to accomplish this through a more complete understanding of the synthesis, structure and function of specific viral proteins that are essential for herpes virus replication. The studies proposed here will be done primarily with cytomegalovirus (CMV) and will focus on: (i) an """"""""early"""""""" nuclear protein that is made in large amounts and binds DNA, (ii) an """"""""immediate-early"""""""" protein that is presumed to modulate the initial stages of the infection cycle, (iii) an assembly protein that appears to be at the center of DNA encapsidation and nucleocapsid envelopment, and (iv) a matrix protein that accumulates to remarkably high levels in the infected cell and is shed into the extracellular environment in the form of virions and dense bodies. We will use wild type and laboratory prototype strains of human CMV in this work, as well as Colburn and several new and old world monkey isolates that have proven valuable for comparative purposes. Our experimental methods will be based on techniques of cell fractionation, particle isolation, affinity and exclusion chromatography, one- and two-dimensional protein and peptide separations, and immunochemistry. Results of these studies will provide information concerning the relatedness of different human CMV isolates to one another and to CMVs from other primates; the molecular composition and organization of the infectious virus particle; and the function of specific proteins in the virus' life cycle. In addition, studies of the inhibitory effect of alpha-difluoro-methylornithine on CMV can be expected to lead to a better understanding of the involvement of polyamines with herpesivirus assembly, and provide some insight into the potential of DFMO as an antiviral drug in man.
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