| The work described in this dissertation was initiated in 2008, shortly after the discovery of Merkel cell polyomavirus (MCV). MCV was discovered as clonally integrated in 80% of Merkel cell carcinoma (MCC) and tumor-derived viral genomes were found to harbor individual large T antigen (LT) truncating deletions. The work presented in this thesis focuses on two main features associated with MCV cell biology: (1) Viral replication requirements that promote viral origin replication in the context of full length MCV LT (chapter 3) and (2) cellular targets that enhance human fibroblast proliferation in the presence of tumor-derived full length LT (chapter 4). As part of these studies, the novel MCV-positive MCC cell line MS-1 was generated, and its cellular and viral features are presented here (chapter 2). MCC cell lines are useful tools that can be used to study MCV biology, and test therapeutic compounds in vitro, as well as in a xenograft setting in vivo as described in the appendix of this thesis. Within the past 6 years, 8 new human polyomaviruses have been identified through basic biological approaches, highlighting the possibility that other human malignancies may be associated with polyomaviral infections. The identification of MCV in association with an aggressive human cancer also underscores the relevance of basic research in understanding human disease. |
