We want to understand functions that are distinctive to human tumor viruses in pre-neoplastic lesions and intumor cells. These functions are potential targets for specific anti-viral therapies to treat viral associatedcancers. We (Drs. Lambert and Sugden) have studied the replication of EBV and HPV for as long as theirplasmid replicons have been known and recently extended our work to include KSHV. The goals of ourresearch have been to characterize in detail the synthesis and partitioning of these viral replicons both tounderstand them in general and to uncover their unique features as targets for anti-viral, anti-tumortherapies. During this funding period we have developed a method to visualize individually EBV's plasmidreplicons in live cells throughout a cell cycle. This approach has revealed a non-random, efficientmechanism for EBV's partitioning and an intrinsic inefficiency in its DNA synthesis. We shall extend thisapproach to study the synthesis and partitioning of intact genomes of EBV, KSHV, and HPV16 in theirnatural host cells. In particular, we shall characterize the replication of EBV during the early steps of itsinfection of primary B-cells to identify its mechanism of establishment, examine the efficiencies of synthesisand partitioning of KSHV as a function of the number of its terminal repeats, and determine the efficienciesand modes of the synthesis and of partitioning of HPV16 in two kinds of epithelial cells. These experimentswill help to define characteristics of the synthesis and partitioning of these human tumor viruses which arelikely distinct from the human genome and thus potential targets for therapeutic intervention.
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