I will continue ongoing studies designed to characterize the mechanism by which the Epstein-Barr nuclear antigen 1 (EBNA-1) protein of Epstein-Barr virus (EBV) facilitates the stable replication of plasmids that bear oriP, EBV's plasmid origin of replication. Together my post-doctoral mentor, Dr. Bill Sugden, and I have demonstrated that oriP-plasmids are synthesized directly by the cell, and that EBNA-1 functions post- synthetically to stabilize oriP-plasmids. Our work also demonstrates that human cells can actively eliminate extra- chromosomal DNAs. This application experimentally addresses the process by which human cells eliminate plasmids, by defining when it occurs in the cell-cycle, and understanding the mechanism by which those viruses that maintain their genomes as plasmids in human cells overcome it. It also experimentally addresses the mechanism by which oriP-plasmids are stabilized so that they can be partitioned faithfully to daughter cells, and the contributions of EBNA-1 to these processes.
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| Chen, Yong; Miller, William M; Aiyar, Ashok (2005) Transduction efficiency of pantropic retroviral vectors is controlled by the envelope plasmid to vector plasmid ratio. Biotechnol Prog 21:274-82 |
| Kikonyogo, A; Bouamr, F; Vana, M L et al. (2001) Proteins related to the Nedd4 family of ubiquitin protein ligases interact with the L domain of Rous sarcoma virus and are required for gag budding from cells. Proc Natl Acad Sci U S A 98:11199-204 |
| Haan, K M; Aiyar, A; Longnecker, R (2001) Establishment of latent Epstein-Barr virus infection and stable episomal maintenance in murine B-cell lines. J Virol 75:3016-20 |
