Undergraduate Honors Theses

Thesis Defended

Spring 2015

Document Type


Type of Thesis

Departmental Honors


Molecular, Cellular, & Developmental Biology

First Advisor

Robert Garcea MD

Second Advisor

Christy Fillman PhD

Third Advisor

Dylan Taatjes PhD

Fourth Advisor

James Goodrich PhD


Polyomaviruses (PyV) efficiently replicate by disrupting host cell signaling pathways. Disruption of the cell cycle is implicated in nearly all tumor formation. Studies of cellular transformation by primate PyV, SV40, and mouse polyomavirus (MPyV) have led to numerous findings concerning tumor suppressor proteins and cell cycle regulation pathways (Das D. and Imperiale 2009, Dahl et. al. 2005). Expression of PyV T Antigens (TAg) modifies signaling pathways and cell cycle checkpoints to the virus’ advantage. Expected modifications include inhibiting checkpoint proteins between G1 and S phases as well as promoting kinases with downstream signaling effects that result in progression to S phase (Fanning et. al. 2009). Unlike in SV40 (Zhao et. al. 2008), the MRN complex has not been found to decrease during infection with MPyV. The presence of mTAg alone has been shown to alter the downstream effects of Akt and TOR pathways in order to initiate cell proliferation and push the cell into S phase, aiding viral replication (Summers et. al. 1998 and Meili et. al. 1998). Presented here is evidence of mTAg activating Akt and TOR in the context of a full MPyV infection. p70 S6 Kinase was also observed to increase levels of activation during MPyV infection. The cell cycle checkpoint regulator p27 was found to be suppressed during MPyV infection, allowing the cell to progress to the S phase. MPyV mTAg is necessary, in tandem with LTAg to alter cell cycle signaling that allows vDNA replication to proceed efficiently.