Project 5

我们的研究发现eb病毒（EBV）的EBNA1蛋白对正常和肿瘤来源的EBV阳性细胞的增殖和存活至关重要。它建立在我们和其他研究人员的发现之上，即EBV基因组中有多个顺式作用元件可以促进染色体外复制。它还包括与博士的合作研究。康普顿和兰伯特检查卡波西肉瘤病毒（KSHV）和人乳头瘤病毒16型（HPV-16）染色体外复制。我们将鉴定和表征EBV DNA中除双对称元（DS）以外的能够支持DNA合成起始的顺式作用元件，并研究KSHV DNA中的类似元件。我们是

The proposed research builds on our findings that the EBNA1 protein of Epstein-Barr Virus (EBV) is pivotal to the proliferation and survival of normal and tumor-derived EBV-positive cells. It builds on our and other researchers' findings that there are multiple cis-acting elements within EBV's genome that can contribute to extrachromosomal replication. It also encompasses collaborative studies with Drs. Compton and Lambert to examine extrachromosomal replication of Kaposi's sarcoma virus (KSHV) and human papillomavirus type 16 (HPV-16). We shall identify and characterize cis-acting elements of EBV DNA other than its dyad symmetry element (DS) that can support initiation of DNA synthesis and study similar elements in KSHV DNA. We are particularly interested in elucidating the mechanisms by which viral replicons are maintained in proliferating cells and shall study the maintenance of EBV-derived plasmids by EBNA1 and the possible contributions of the E2 protein to the maintenance of HPV16-derived plasmids. These studies are driven by the hypothesis that the inhibition of maintenance functions of human tumor viruses should permit the development of rational, effective therapies for their associated tumors. Both EBNA1 of EBV and LANA1 of KSHV inhibit apoptosis. We propose to identify the mechanisms by which they do so. It is possible that blocking this inhibition would also be therapeutically beneficial for treating EBV- and KSHV-associated tumors.