Date of Award

12-2013

Degree Name

Doctor of Philosophy

Department

Biological Sciences

First Advisor

Dr. Bruce Bejcek

Second Advisor

Dr. John Geiser

Third Advisor

Dr. Neal Goodwin

Abstract

Due to the complex nature of cancer, a variety of strategies are being employed to treat patients. Among these are oncolytic viruses that conditionally replicate in tumor cells with specific cellular landscapes. Several viruses including Herpesviruses, Adenoviruses, and Poxviruses, predominantly vaccinia virus (VV), have been explored for their oncolytic potential. Most of these viruses can productively infect a variety of cell types and it is one goal to create conditionally lethal viruses that can only replicate in tumor cells. Due to the prevalence of p53 inactivating mutations in cancers viruses that are restricted to p53 null cells are desirable and have been developed. We were interested if we could develop a similar mutant in the tanapox virus. Here we describe the identification of a protein from the 142R open reading frame of the tanapox virus genome that is orthologous to the B1R protein from VV which is known to down regulate p53 by phosphorylation. We determine that like B1R, TPV142R encodes a serine threonine kinase that can phosphorylate the tumor suppressor p53. However, we were not able to isolate a TPV142R knockout virus using our current system of viral mutant generation indicating that the p142R protein is essential for viral replication. This was confirmed by using shRNA to target the knockdown of 142R which resulted in a decrease in viral replication. Due to the apparent necessary function that 142R protein provides, TPV lacking 142R may not make a suitable oncolytic virus.

Access Setting

Dissertation-Open Access

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